A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 3 and CASPASE 10. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
A family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS. Caspase 10 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Several isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 12 is activated by pro-apoptotic factors that are released during cell stress and by CARD SIGNALING ADAPTOR PROTEINS. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
A short pro-domain caspase that is almost exclusively expressed in the EPIDERMIS and may play a role in the differentiation of epidermal KERATINOCYTES.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)
An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
A CARD signaling adaptor protein that plays a role in the mitochondria-stimulated apoptosis (APOPTOSIS, INTRINSIC PATHWAY). It binds to CYTOCHROME C in the CYTOSOL to form an APOPTOSOMAL PROTEIN COMPLEX and activates INITIATOR CASPASES such as CASPASE 9.
A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
A subtype of caspases that contain long pro-domain regions that regulate the activation of the enzyme. The pro-domain regions contain protein-protein interaction motifs that can interact with specific signaling adaptor proteins such as DEATH DOMAIN RECEPTORS; DED SIGNALING ADAPTOR PROTEINS; and CARD SIGNALING ADAPTOR PROTEINS. Once activated, the initiator caspases can activate other caspases such as the EFFECTOR CASPASES.
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A member of the Bcl-2 protein family that reversibly binds MEMBRANES. It is a pro-apoptotic protein that is activated by caspase cleavage.
A large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cell line derived from cultured tumor cells.
ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
Peptides composed of between two and twelve amino acids.
A signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Established cell cultures that have the potential to propagate indefinitely.
A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
The voltage difference, normally maintained at approximately -180mV, across the INNER MITOCHONDRIAL MEMBRANE, by a net movement of positive charge across the membrane. It is a major component of the PROTON MOTIVE FORCE in MITOCHONDRIA used to drive the synthesis of ATP.
Transport proteins that carry specific substances in the blood or across cell membranes.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
Physiologically inactive substances that can be converted to active enzymes.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
The pathological process occurring in cells that are dying from irreparable injuries. It is caused by the progressive, uncontrolled action of degradative ENZYMES, leading to MITOCHONDRIAL SWELLING, nuclear flocculation, and cell lysis. It is distinct it from APOPTOSIS, which is a normal, regulated cellular process.
A subclass of caspases that contain short pro-domain regions. They are activated by the proteolytic action of INITIATOR CASPASES. Once activated they cleave a variety of substrates that cause APOPTOSIS.
Multimeric protein complexes formed in the CYTOSOL that play a role in the activation of APOPTOSIS. They can occur when MITOCHONDRIA become damaged due to cell stress and release CYTOCHROME C. Cytosolic cytochrome C associates with APOPTOTIC PROTEASE-ACTIVATING FACTOR 1 to form the apoptosomal protein complex. The apoptosome signals apoptosis by binding to and activating specific INITIATOR CASPASES such as CASPASE 9.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A death domain receptor signaling adaptor protein that plays a role in signaling the activation of INITIATOR CASPASES such as CASPASE 2. It contains a death domain that is specific for RIP SERINE-THEONINE KINASES and a caspase-binding domain that binds to and activates CASPASES such as CASPASE 2.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.
A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
A multi-domain mitochondrial membrane protein and member of the bcl-2 Protein family. Bak protein interacts with TUMOR SUPPRESSOR PROTEIN P53 and promotes APOPTOSIS.
Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.
A family of serine endopeptidases found in the SECRETORY GRANULES of LEUKOCYTES such as CYTOTOXIC T-LYMPHOCYTES and NATURAL KILLER CELLS. When secreted into the intercellular space granzymes act to eliminate transformed and virus-infected host cells.
Elements of limited time intervals, contributing to particular results or situations.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Proteins encoded by the mitochondrial genome or proteins encoded by the nuclear genome that are imported to and resident in the MITOCHONDRIA.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A family of serine-threonine kinases that plays a role in intracellular signal transduction by interacting with a variety of signaling adaptor proteins such as CRADD SIGNALING ADAPTOR PROTEIN; TNF RECEPTOR-ASSOCIATED FACTOR 2; and TNF RECEPTOR-ASSOCIATED DEATH DOMAIN PROTEIN. Although they were initially described as death domain-binding adaptor proteins, members of this family may contain other protein-binding domains such as those involving caspase activation and recruitment.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.
Tumor necrosis factor receptor family members that are widely expressed and play a role in regulation of peripheral immune responses and APOPTOSIS. The receptors are specific for TNF-RELATED APOPTOSIS-INDUCING LIGAND and signal via conserved death domains that associate with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Glycoproteins found on the membrane or surface of cells.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
A pro-apoptotic protein and member of the Bcl-2 protein family that is regulated by PHOSPHORYLATION. Unphosphorylated Bad protein inhibits the activity of BCL-XL PROTEIN.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A family of serine proteinase inhibitors which are similar in amino acid sequence and mechanism of inhibition, but differ in their specificity toward proteolytic enzymes. This family includes alpha 1-antitrypsin, angiotensinogen, ovalbumin, antiplasmin, alpha 1-antichymotrypsin, thyroxine-binding protein, complement 1 inactivators, antithrombin III, heparin cofactor II, plasminogen inactivators, gene Y protein, placental plasminogen activator inhibitor, and barley Z protein. Some members of the serpin family may be substrates rather than inhibitors of SERINE ENDOPEPTIDASES, and some serpins occur in plants where their function is not known.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
A human cell line established from a diffuse histiocytic lymphoma (HISTIOCYTIC LYMPHOMA, DIFFUSE) and displaying many monocytic characteristics. It serves as an in vitro model for MONOCYTE and MACROPHAGE differentiation.
The B-cell leukemia/lymphoma-2 genes, responsible for blocking apoptosis in normal cells, and associated with follicular lymphoma when overexpressed. Overexpression results from the t(14;18) translocation. The human c-bcl-2 gene is located at 18q24 on the long arm of chromosome 18.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
The two lipoprotein layers in the MITOCHONDRION. The outer membrane encloses the entire mitochondrion and contains channels with TRANSPORT PROTEINS to move molecules and ions in and out of the organelle. The inner membrane folds into cristae and contains many ENZYMES important to cell METABOLISM and energy production (MITOCHONDRIAL ATP SYNTHASE).
Proteins prepared by recombinant DNA technology.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Members of the class of neutral glycosphingolipids. They are the basic units of SPHINGOLIPIDS. They are sphingoids attached via their amino groups to a long chain fatty acyl group. They abnormally accumulate in FABRY DISEASE.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A RIP serine-theonine kinase that contains a C-terminal caspase activation and recruitment domain. It can signal by associating with other CARD-signaling adaptor proteins and INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.
The action of a drug in promoting or enhancing the effectiveness of another drug.
A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
The segregation and degradation of damaged or unwanted cytoplasmic constituents by autophagic vacuoles (cytolysosomes) composed of LYSOSOMES containing cellular components in the process of digestion; it plays an important role in BIOLOGICAL METAMORPHOSIS of amphibians, in the removal of bone by osteoclasts, and in the degradation of normal cell components in nutritional deficiency states.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.
A family of cell surface receptors that signal via a conserved domain that extends into the cell CYTOPLASM. The conserved domain is referred to as a death domain due to the fact that many of these receptors are involved in signaling APOPTOSIS. Several DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS can bind to the death domains of the activated receptors and through a complex series of interactions activate apoptotic mediators such as CASPASES.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Compounds that inhibit cell production of DNA or RNA.
A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
The N-acetyl derivative of CYSTEINE. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates.
A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.
Proteins found in any species of virus.
The process of cleaving a chemical compound by the addition of a molecule of water.
A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)
That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Preparations of cell constituents or subcellular materials, isolates, or substances.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.
Adenine nucleotides which contain deoxyribose as the sugar moiety.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
Nuclear matrix proteins that are structural components of the NUCLEAR LAMINA. They are found in most multicellular organisms.
A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Proteins found in any species of insect.
High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.
Property of membranes and other structures to permit passage of light, heat, gases, liquids, metabolites, and mineral ions.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
A lysosomal cysteine proteinase with a specificity similar to that of PAPAIN. The enzyme is present in a variety of tissues and is important in many physiological and pathological processes. In pathology, cathepsin B has been found to be involved in DEMYELINATION; EMPHYSEMA; RHEUMATOID ARTHRITIS, and NEOPLASM INVASIVENESS.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
An antibiotic produced by Pseudomonas cocovenenans. It is an inhibitor of MITOCHONDRIAL ADP, ATP TRANSLOCASES. Specifically, it blocks adenine nucleotide efflux from mitochondria by enhancing membrane binding.
The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN.
The process by which chemical compounds provide protection to cells against harmful agents.
One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.
A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A subclass of ubiquitously-expressed lamins having an acidic isoelectric point. They are found to remain bound to nuclear membranes during mitosis.
An indole-dione that is obtained by oxidation of indigo blue. It is a MONOAMINE OXIDASE INHIBITOR and high levels have been found in urine of PARKINSONISM patients.
A type I keratin found associated with KERATIN-8 in simple, or predominately single layered, internal epithelia.
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)
A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.
A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)
Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.

MycN sensitizes neuroblastoma cells for drug-induced apoptosis. (1/2233)

Amplification of the MYCN gene is found in a large proportion of neuroblastoma and considered as an adverse prognostic factor. To investigate the effect of ectopic MycN expression on the susceptibility of neuroblastoma cells to cytotoxic drugs we used a human neuroblastoma cell line harboring tetracycline-controlled expression of MycN. Neither conditional expression of MycN alone nor low drug concentrations triggered apoptosis. However, when acting in concert, MycN and cytotoxic drugs efficiently induced cell death. Apoptosis depended on mitochondrial permeability transition and activation of caspases, since the mitochondrion-specific inhibitor bongkrekic acid and the caspase inhibitor zVAD-fmk almost completely abrogated apoptosis. Loss of mitochondrial transmembrane potential and release of cytochrome c from mitochondria preceded activation of caspase-8 and caspase-3 and cleavage of PARP. CD95 expression was upregulated by treatment with cytotoxic drugs, while MycN cooperated with cytotoxic drugs to increase sensitivity to CD95-induced apoptosis and enhancing CD95-L expression. MycN overexpression and cytotoxic drugs also synergized to induce p53 and Bax protein expression, while Bcl-2 and Bcl-X(L) protein levels remained unchanged. Since amplification of MYCN is usually associated with a poor prognosis, these findings suggest that dysfunctions in apoptosis pathways may be a mechanism by which MycN-induced apoptosis of neuroblastoma cells is inhibited.  (+info)

Identification of an endogenous dominant-negative short isoform of caspase-9 that can regulate apoptosis. (2/2233)

Alternatively spliced isoforms of certain apoptosis regulators, such as Bcl-x, Ced-4, and Ich-1, have been shown to play opposing roles in regulating apoptosis. Here, we describe the identification of an endogenous alternatively spliced isoform of caspase-9, named caspase-9b, which lacks the central large subunit caspase domain. Caspase-9b is detectable in many cell lines by PCR and at the mRNA and protein levels. Caspase-9b can interact with the caspase recruitment domain of Apaf-1, and like the active site mutant of caspase-9, it can inhibit multiple forms of apoptosis, including those triggered by oligomerization of death receptors. It can also block activation of caspase-9 and -3 by Apaf-1 in an in vitro cytochrome c-dependent caspase activation assay. These results suggest that caspase-9b functions as an endogenous apoptosis inhibitory molecule by interfering with the formation of a functional Apaf-1-caspase-9 complex.  (+info)

Caspase-9 can be activated without proteolytic processing. (3/2233)

The recombinant form of the proapoptotic caspase-9 purified following expression in Escherichia coli is processed at Asp315, but largely inactive; however, when added to cytosolic extracts of human 293 cells it is activated 2000-fold in the presence of cytochrome c and dATP. Thus, the characteristic activities of caspase-9 are context-dependent, and its activation may not recapitulate conventional caspase activation mechanisms. To explore this hypothesis we produced recombinant forms of procaspase-9 containing mutations that disabled one or both of the interdomain processing sites of the zymogen. These mutants were able to activate downstream caspases, but only in the presence of cytosolic factors. The mutant with both processing sites abolished had 10% of the activity of wild-type, and was able to support apoptosis, with equal vigor to wild-type, when transiently expressed in 293 cells. Thus caspase-9 has an unusually active zymogen that does not require proteolytic processing, but instead is dependent on cytosolic factors for expression of its activity.  (+info)

Tumor necrosis factor alpha regulation of the FAS-mediated apoptosis-signaling pathway in synovial cells. (4/2233)

OBJECTIVE: Fas-mediated apoptosis is observed in synoviocytes of patients with rheumatoid arthritis (RA), but not in those of patients with osteoarthritis (OA). The present study was conducted to elucidate the mechanisms that initiate induction of Fas-mediated apoptosis in RA synoviocytes. METHODS: Cultured OA synoviocytes, which are insensitive to Fas-mediated apoptosis in spite of Fas antigen expression, were used in these experiments. Synovial cell proliferation and cytotoxicity studies were performed using MTS and lactate dehydrogenase release assays. Surface expression of Fas antigen was analyzed by flow cytometry. The expression and function of apoptosis-signaling molecules, such as caspase 8 and caspase 3, were examined by immunoblot analysis. RESULTS: Tumor necrosis factor alpha (TNFalpha) induced proliferation of cultured OA synoviocytes. Fas ligation with anti-Fas monoclonal antibody (mAb) resulted in cytotoxic activity against cultured OA synoviocytes that had been pretreated with TNFalpha for 5 days, but not those pretreated for 2 days. In contrast, anti-Fas mAb did not show a cytotoxic effect against untreated cultured OA synoviocytes. A gradual up-regulation of caspase 8 and caspase 3, which played a role in the caspase cascade for Fas-mediated apoptosis, was observed in TNFalpha-treated cultured OA synoviocytes. In addition, Fas ligation to TNFalpha-treated cultured OA synoviocytes induced activation of caspase 8 and caspase 3, with subsequent cleavage of poly(ADP-ribose) polymerase (PARP), a substrate of activated caspase 3. More importantly, Z-IETD-FMK, a caspase 8 inhibitor, and Ac-DEVD-CHO, a caspase 3 inhibitor, almost completely inhibited Fas-mediated apoptosis of TNFalpha-treated cultured OA synoviocytes, whereas Ac-YVAD-CHO, a caspase 1 inhibitor, did not. CONCLUSION: Our results clearly demonstrate that TNFalpha stimulates synovial cells to proliferate as well as sensitizes the cells for Fas-mediated apoptosis, at least in part by up-regulation and activation of caspase 8 and caspase 3. These findings suggest that TNFalpha may be one of the factors providing sensitization of synovial cells to Fas-mediated apoptosis in RA.  (+info)

Solution structure of BID, an intracellular amplifier of apoptotic signaling. (5/2233)

We report the solution structure of BID, an intracellular cross-talk agent that can amplify FAS/TNF apoptotic signal through the mitochondria death pathway after Caspase 8 cleavage. BID contains eight alpha helices where two central hydrophobic helices are surrounded by six amphipathic ones. The fold resembles poreforming bacterial toxins and shows similarity to BCL-XL although sequence homology to BCL-XL is limited to the 16-residue BH3 domain. Furthermore, we modeled a complex of BCL-XL and BID by aligning the BID and BAK BH3 motifs in the known BCL-XL-BAK BH3 complex. Additionally, we show that the overall structure of BID is preserved after cleavage by Caspase 8. We propose that BID has both BH3 domain-dependent and -independent modes of action in inducing mitochondrial damage.  (+info)

Solution structure of the proapoptotic molecule BID: a structural basis for apoptotic agonists and antagonists. (6/2233)

Members of the BCL2 family of proteins are key regulators of programmed cell death, acting either as apoptotic agonists or antagonists. Here we describe the solution structure of BID, presenting the structure of a proapoptotic BCL2 family member. An analysis of sequence/structure of BCL2 family members allows us to define a structural superfamily, which has implications for general mechanisms for regulating proapoptotic activity. It appears two criteria must be met for proapoptotic function within the BCL2 family: targeting of molecules to intracellular membranes, and exposure of the BH3 death domain. BID's activity is regulated by a Caspase 8-mediated cleavage event, exposing the BH3 domain and significantly changing the surface charge and hydrophobicity, resulting in a change of cellular localization.  (+info)

Nitric-oxide-induced apoptosis in human leukemic lines requires mitochondrial lipid degradation and cytochrome C release. (7/2233)

We have previously shown that nitric oxide (NO) stimulates apoptosis in different human neoplastic lymphoid cell lines through activation of caspases not only via CD95/CD95L interaction, but also independently of such death receptors. Here we investigated mitochondria-dependent mechanisms of NO-induced apoptosis in Jurkat leukemic cells. NO donor glycerol trinitrate (at the concentration, which induces apoptotic cell death) caused (1) a significant decrease in the concentration of cardiolipin, a major mitochondrial lipid; (2) a downregulation in respiratory chain complex activities; (3) a release of the mitochondrial protein cytochrome c into the cytosol; and (4) an activation of caspase-9 and caspase-3. These changes were accompanied by an increase in the number of cells with low mitochondrial transmembrane potential and with a high level of reactive oxygen species production. Higher resistance of the CD95-resistant Jurkat subclone (APO-R) cells to NO-mediated apoptosis correlated with the absence of cytochrome c release and with less alterations in other mitochondrial parameters. An inhibitor of lipid peroxidation, trolox, significantly suppressed NO-mediated apoptosis in APO-S Jurkat cells, whereas bongkrekic acid (BA), which blocks mitochondrial permeability transition, provided only a moderate antiapoptotic effect. Transfection of Jurkat cells with bcl-2 led to a complete block of apoptosis due to the prevention of changes in mitochondrial functions. We suggest that the mitochondrial damage (in particular, cardiolipin degradation and cytochrome c release) induced by NO in human leukemia cells plays a crucial role in the subsequent activation of caspase and apoptosis.  (+info)

Targeted disruption of caspase genes in mice: what they tell us about the functions of individual caspases in apoptosis. (8/2233)

Cysteine proteases of the caspase family are crucial mediators of apoptosis. All mammalian cells contain a large number of caspases. Although many caspases are activated in a cell committed to apoptosis, recent data from caspase gene knockout mice suggest that individual caspases may be involved in the cell and stimulus-specific pathways of cell death. The gene disruption studies also establish the functional hierarchy between two structurally distinct classes of caspases. The present review discusses these recent findings and elaborates on how these mutant mouse models have helped the understanding of the mechanisms that govern programmed cell death in the immune and other systems.  (+info)

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Antho 50 induces caspase 3 activation and UHRF1 down-regulation independently of p53 and p73.B CLL cells were incubated with Antho 50 at 75 μg/mL for the ind
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The IUPHAR/BPS Guide to Pharmacology. Caspase 1 - C14: Caspase. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Caspase detection antibodies and assays are used to help detect and study caspase activation in Apoptotic cells via immunoprecipitation and immunoblotting techniques.
Caspase 8 enzymatic activity in rat retinas. A: The level of protein expression of caspase 8 in the rat retina was evaluated by western blotting. Diabetes incre
A long pro-domain caspase that has specificity for the precursor form of INTERLEUKIN-1BETA. It plays a role in INFLAMMATION by catalytically converting the inactive forms of CYTOKINES such as interleukin-1beta to their active, secreted form. Caspase 1 is referred as interleukin-1beta converting enzyme and is frequently abbreviated ICE ...
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BioAssay record AID 306845 submitted by ChEMBL: Induction of apoptosis in U937 cells assessed as caspase 3 cleavage at 3 uM by Western blot.
The intracellular redox position is intently connected to the levels of professional-inflammatory cytokines, IL-1β, IL-23 and TNF-α which are the major factors of inflammatory responses. IFN-γ has also been shown to be linked with swelling although TNF-α has been researched thoroughly for its function in the inflammatory method and generation of ROS.Maintaining the earlier mentioned information into thought, we evaluated the level of IL-1β and IL-seventeen employing ELISA even though IFN-γ, IL-23 and TNF-α mRNA expression fold transform was identified utilizing qRT-PCR. We located that IL-1β ranges had been considerably larger in the two diabetic teams as in MEDChem Express 415903-37-6 contrast to the wholesome handle topics. The IL-1β is typically expressed by in-filtering macrophages, once activated they synthesize larger volume of nitric oxide as well. Curiously, there have been outstanding discrepancies in both NO and cytokine levels in the patients of higher age teams with glucose ...
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TY - CHAP. T1 - Pyroptosis. AU - Lawlor, Kathryn. AU - Conos, Stephanie A.. AU - Vince, James E. PY - 2018/12/9. Y1 - 2018/12/9. N2 - Pyroptosis is considered an inflammatory cell death pathway that can be triggered by caspase‐1 or caspase‐11, or the human caspase‐11 orthologs, caspase‐4 and caspase‐5. The activation of caspase‐1 is mediated by supramolecular cytosolic protein complexes, termed inflammasomes, which sense specific pathogen, host or environmental danger molecules. Prior to causing pyroptotic death, caspase‐1 can also cleave and thereby activate the potent pro‐inflammatory cytokines, interleukin‐1 (IL‐1 ) and IL‐18. In contrast, the activation of caspase‐11 is caused by its direct binding to cytosolic lipopolysaccharide (LPS) derived from gram‐negative bacteria. While caspase‐11 can promote caspase‐1 activity, caspase‐1 is not required for caspase‐11 killing, and caspase‐11 itself does not efficiently activate IL‐1 or IL‐18. Unlike apoptotic ...
The apoptotic protease-activating factor 1 (Apaf-1) split luciferase biosensor continues to be used like a biological tool for the detection of early stage of apoptosis. and in human being diseases, the systems involved in this technique and the advancement of assays to recognize drug-like molecules that could be therapeutically useful possess drawn a whole lot of interest in the field. To day, many assays ideal for high-throughput testing have already been used and made for the detection of apoptosis. Each one uses particular feature of apoptosis pathway (whether intrinsic or extrinsic). Nevertheless, until the advancement of the Apaf-1 break up luciferase complementary assay, non-e could be utilized to monitor apoptosome development inside the cell loss of life signaling pathway [7,8,9]. With this novel split luciferase reporter, Nluc/Apaf-1 and Cluc/Apaf-1, the N-terminal and C-terminal fragments of luciferase, are genetically fused to the N-terminal site of Apaf-1 [10,11]. Here, we extended ...
Caspase 3 antibody LS-C88630 is a biotin-conjugated rabbit polyclonal that binds human, mouse, rat, bovine, dog, hamster, pig, rabbit, and sheep caspase 3 (also known as CASP3). Caspase 3 antibody is validated for use in IHC-paraffin, immunoprecipitation, and western blot.
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This video will show you how to perform an apoptosis assay using adherent cells on the Celigo image cytometer using caspase 3/7 and Hoechst reagents.
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Induction of apoptosis and NF-kB activation by Apaf-1/Nod1 family members and DD proteins (Inohara et al., 2000). The more recent study suggested that IKKgamma binds to the site in C-terminal regulatory region of IKKbeta which is located after the HLH motif. Images ...
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Apoptosis is a controlled form of cellular demolition, catalyzed by a family of cysteine proteases called caspases. In response to diverse proapoptotic stimuli, caspase-9 is recruited and activated within an oligomeric complex called the apoptosome. The apoptosome drives autocatalytic processing of caspase-9, triggering a proteolytic caspase cascade that results in the biochemical and morphological changes characteristic of cell death. It is unclear why caspase-9 undergoes autocatalytic processing following apoptosome recruitment, because interdomain processing is dispensable for caspase-9 activity. A study has shed light on this issue by demonstrating that caspase-9 processing within the apoptosome promotes its displacement from the complex, leading to inactivation of this protease. Thus, autoprocessing of caspase-9 within the apoptosome serves as a molecular timer that limits the proteolytic activity of this complex through displacement of bound caspase-9 molecules. This timer mechanism may ...
Caspase-6 is an enzyme that in humans is encoded by the CASP6 gene. CASP6 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. Caspase-6 has known functions in apoptosis, early immune response and neurodegenration in Huntingtons and Alzheimers disease. This gene encodes a protein that is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein is processed by caspases 7, 8 and 10, and is thought to function as a downstream enzyme in the caspase activation cascade. Caspase 6 can also undergo self-processing without other members of the caspase family. Alternative ...
Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. It is encoded by the CASP3 gene. CASP3 orthologs have been identified in numerous mammals for which complete genome data are available. Unique orthologs are also present in birds, lizards, lissamphibians, and teleosts. The CASP3 protein is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 6 and 7; and the protein itself is processed and activated by caspases 8, 9, and 10. It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimers disease. Alternative splicing of this gene results in two ...
CASP10; MCH4; Caspase-10; CASP-10; Apoptotic protease Mch-4; FAS-associated death domain protein interleukin-1B-converting enzyme 2; FLICE2; ICE-like apoptotic protease ...
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Active Caspase 2 FITC Staining Kit (ab65612). Active caspase 2 detection in living cells by flow, microscopy or fluorescent plate reader.
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BioAssay record AID 675053 submitted by ChEMBL: Induction of apoptosis in human SW620 cells assessed as activation of caspase 3/7 at 100 uM after 24 hrs by luminescence assay.
Apoptosis or programmed death is a physiological process responsible for normal development and homeostasis of multicellular organisms. This process involves a well-functioning machinery of death, which are the main component of cysteine ​​proteases - caspases family. These enzymes are present in cells in a latent form and become activated during apoptosis induced by various factors. This review summarizes the progress made on structure, mechanism of activation, catalytic properties, are substrates of caspases and regulation of their activity. Also shown in the involvement of caspases in the major pathways of apoptosis.. ...
Human caspase 2 ELISA kit can be used for detecting in vitro quantitative levels of caspase-2 (CASP2) in human serum, cell culture supernatant, plasma, tissue
Read independent reviews on Caspase Fluorometric Substrate Set II Plus from AMS Biotechnology (Archived Products) on SelectScience
72 products from 18 suppliers. Compare and order Caspase 8 ELISA Kits. View citations, images, detection ranges, sensitivity, prices and more. Recommended products for the most popular species. Our scientists will help you find the right ELISA kit for your needs.
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TY - JOUR. T1 - Cisplatin-induced apoptosis in p53-deficient renal cells via the intrinsic mitochondrial pathway. AU - Jiang, Man. AU - Wang, Cong Yi. AU - Huang, Shuang. AU - Yang, Tianxin. AU - Dong, Zheng. N1 - Copyright: Copyright 2009 Elsevier B.V., All rights reserved.. PY - 2009/5. Y1 - 2009/5. N2 - Nephrotoxicity is the major limiting factor for the use of cisplatin in cancer therapy. Recent studies have demonstrated an important role for p53 in cisplatin-induced renal injury. Nevertheless, pharmacological and genetic blockade of p53 only provides partial renoprotective effects, suggesting the presence of p53-independent injury mechanisms. To understand the p53-independent mechanisms, we have now examined cisplatin-induced apoptosis in p53-deficient kidney cells. We show that cisplatin could induce Bax activation, cytochrome c release, and apoptosis in primary cultures of p53-deficient renal tubular cells, albeit at a level that was lower than in the wild-type cells. Cisplatin could also ...
Assay Kits , Caspase Assay Kits , SensoLyte AFC Caspase Profiling Kit *Fluorimetric*; Caspases play important roles in apoptosis and cell signaling. They are also identified as drug-screening targets. AFC-based substrates yield blue fluorescence upon protease cleavage. They are widely used to monitor caspase activity. The SensoLyte Caspase Profiling Kit contains a series of AFC-based peptide substrates (Ex/Em=380 nm/500 nm) as fluorogenic indicators for assaying caspase protease activities. The kit contains a well-designed plate in which a series of AFC-based caspase substrates are coated with both positive and negative controls. It provides the best solution for profiling caspases or caspase inhibitors. The kit contains: A 96-well plate coated with a series of AFC-based caspase substrates along with various controls* Cell lysis buffer Assay buffer AFC (fluorescence reference standard for calibration) A detailed protocol A detailed protocol
Caspase inhibition is effective in minimizing nucleosome accumulation in key cortical cultures stimulated by TNF and thrombin. In contrast, the exact same effect is simply not observed in differentiated PC12 cells. In PC12 cells TNF induced LDH release is decreased by caspase inhibition. For the reason that TNF remedy induces both LDH release and nucleosome accumulation in PC12 cells, caspase inhibition could possibly enrich cell survival below disorders that induce a mixed apoptotic necrotic response. Pytlowany and colleagues demonstrate that In PC12 cells NO released from SNP decreases cell viability inside a time and concentration dependent method, with a increased concentration of NO leading to immediate and sustained lower in cell survival with no evoking a corresponding immediate activation of caspase three . In the recent review we locate that NO created by 0.5 mM SNP activates caspase three inside a longer time frame ...
TY - JOUR. T1 - Protective effect of resveratrol against caspase 3 activation in primary mouse fibroblasts. AU - Ulakcsai, Zsófia. AU - Bagaméry, Fruzsina. AU - Vincze, István. AU - Szöko, Éva. AU - Tábi, Tamás. PY - 2015/1/1. Y1 - 2015/1/1. N2 - Aim: To study the effect of resveratrol on survival and caspase 3 activation in non-transformed cells after serum deprivation. Methods: Apoptosis was induced by serum deprivation in primary mouse embryonic fibroblasts. Caspase 3 activation and lactate dehydrogenase release were assayed as cell viability measure by using their fluorogenic substrates. The involvement of PI3K, ERK, JNK, p38, and SIRT1 signaling pathways was also examined. Results: Serum deprivation of primary fibroblasts induced significant activation of caspase 3 within 3 hours and reduced cell viability after 24 hours. Resveratrol dose-dependently prevented caspase activation and improved cell viability with 50% inhibitory concentration (IC50) = 66.3 ± 13.81 μM. It also reduced ...
Fluorescent Dyes , Enzyme Detection Reagents , Caspase 3 (Apopain) Substrate 1r-z, fluorogenic; Rh110 (rhodamine 110)-derived caspase substrates are probably the most sensitive indicators widely used for the fluorimetric detection of various caspase activities. Cleavage of Rh110 peptides by caspases generates strongly fluorescent Rh110 that is monitored fluorimetrically at 510-530 nm with excitation of 488 nm, the most common excitation light source used in fluorescence instruments.; Caspase-3 substrate and caspase-7 substrate; (Z-DEVD)2-Rh110; z-(Asp-Glu-Val-Asp)2-Rh110
Caspase 3/7 Glo assay from Promega - posted in Apoptosis, Necrosis and Autophagy: Hello all, I recently purchased a Caspase 3/7 Glo assay kit from Promega for apoptosis detection.My assay was done with HEK293 cells which were stimulated with Etoposide.I performed the assay exactly described in the protocol,and detected the luminescence with our Luminoskan Ascent luminometer. Unfortunately, in my assay I observed no induction of caspase activity and that the highest reading was equal to the...
Severn Biotech, Limited SBP0058 - Caspase 1 Inhibitor Ac-YVAD aldehyde - SBP0058 - Caspase 1 Inhibitor Ac-YVAD aldehyde MW: 492.5 Ac-Tyr-Val-Ala-Asp-CHO A specific reversible inhibitor of caspase 1 (ICE, Interleukin 1ß Converting Enzyme) Thornberry N.A. et al. (1992) Nature 356, 768; Molineaux S.M. et al. (1993) Proc. Natl. Acad. Sci. USA 90, 1809; Walker N.P.C. et al. (1994) Cell 78, 343; Wilson K.P. et al. (1994) Nature 370, 270;
Generic Caspase Activity Assay Kit (Fluorometric - Green) (ab112130). Detect generic caspase activation in live cells with green TF2-VAD-FMK substrate.
Death receptor (DR) ligation can lead to divergent signaling pathways causing either caspase-mediated cell death or cell proliferation and inflammation. These variations in cellular fate are determined by adaptor proteins that are recruited to the DR signaling complex. FLICE inhibitory protein (FLIP) is an established inhibitor of caspase-8-mediated apoptosis, and it is also involved in NF-kappa B
Caspase Substrate Assay Kit (Colorimetric) is used for assaying activities of members of caspase 1/2/3/5/6/8/9. (KA3698) - Products - Abnova
Release of cytochrome c from mitochondria by apoptotic signals induces ATP/dATP-dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. Here we show that the documented anti-apoptotic effect of the principal heat-shock protein, Hsp70, is mediated through its direct association with the ca …
Kumar, A.P., Chang, M.K.X., Clement, M.-V., Fliegel, L., Pervaiz, S. (2007). Oxidative repression of NHE1 gene expression involves iron-mediated caspase activity. Cell Death and Differentiation 14 (10) : 1733-1746. [email protected] Repository. https://doi.org/10.1038/sj.cdd. ...
Death Check I Assay System (TUNEL/Caspase) from Promega,Apoptosis Detection Systems and Reagents,biological,biology supply,biology supplies,biology product
F CD8+ T lymphocytes before operation, but this difference was not statistically BI 78D3 Significant (P.0.05). The percentages of CD8+ T lymphocytes in the
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Plasmid pcDNA-Caspase 12 from Dr. Junying Yuans lab contains the insert Caspase 12 and is published in Nature. 2000 Jan 6. 403(6765):98-103. This plasmid is available through Addgene.
... hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner". The Journal of Cell Biology. ... Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 ... Hu Y, Benedict MA, Wu D, Inohara N, Núñez G (Apr 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 ... Activated caspase-9 stimulates the subsequent caspase cascade that commits the cell to apoptosis. Alternative splicing results ...
2005) XIAP inhibits caspase-3 and -7 using two binding sites: evolutionarily conserved mechanism of IAPs. EMBO J 24: 645-655 ... 2006) The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J Biol Chem 281: 3254-3260 Pop C, ... His research focuses on proteases and their inhibitors in humans, with particular emphasis on the caspases of the apoptotic ... 2006) The apoptosome activates caspase-9 by dimerization. Mol Cell 22: 269-275 Eckelman BP, Salvesen GS. ( ...
Caspase recruitment domain-containing protein 9 is an adaptor protein of the CARD-CC protein family, which in humans is encoded ... "Entrez Gene: CARD9 caspase recruitment domain family, member 9". Bertin J, Guo Y, Wang L, Srinivasula SM, Jacobson MD, Poyet JL ... CARD9 is a member of the CARD protein family, which is defined by the presence of a characteristic caspase-associated ... Merriam S, Du MQ, Dyer MJ, Robison KE, DiStefano PS, Alnemri ES (December 2000). "CARD9 is a novel caspase recruitment domain- ...
Rho inactivation can activate caspase-3 and caspase-9; two key components of the apoptotic pathway. TcdA has been linked to ... 50 (7): 613-9. doi:10.1099/0022-1317-50-7-613. PMID 11444771. Kuehne SA, Cartman ST, Heap JT, Kelly ML, Cockayne A, Minton NP ( ... 62 (2): 384-9. doi:10.1128/IAI.62.2.384-389.1994. PMC 186119. PMID 8300199. Hecht G, Pothoulakis C, LaMont JT, Madara JL ( ... 458 (7242): 1176-9. Bibcode:2009Natur.458.1176L. doi:10.1038/nature07822. PMC 2679968. PMID 19252482.. ...
Weng C, Li Y, Xu D, Shi Y, Tang H (Mar 2005). "Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related ... Pan G, O'Rourke K, Dixit VM (Mar 1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". The Journal of Biological ... "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". Proceedings of the National Academy of ... 12 (9): 1432-40. doi:10.1210/mend.12.9.0166. PMID 9731710. Ray R, Chen G, Vande Velde C, Cizeau J, Park JH, Reed JC, Gietz RD, ...
The NLRP1 protein interacts strongly with caspase 2 and weakly with caspase 9. Overexpression of this gene was demonstrated to ... responsible for the recruitment and activation of pro-caspase-1 in the active form of caspase-1. Human NLRP1 activation can be ... NLRP1 has been shown to interact with caspase 9 and APAF1. Via its FIIND domain, NLRP1 interacts directly with DPP9 and DPP8 ... Ced-family members contain a caspase recruitment domain (CARD) and are known to be key mediators of programmed cell death. The ...
Pan G, O'Rourke K, Dixit VM (1998). "Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex". J. Biol. Chem. 273 (10): 5841-5. ... The mouse counterpart of this protein is found to interact with Apaf1 and forms a protein complex with Caspase 9, which ... 8 (2): 83-9. doi:10.1007/s101470300015. PMID 12720100. Kang Y, Lee DC, Han J, et al. (2007). "NM23-H2 involves in negative ... 87 (9): 923-40. doi:10.1007/s00109-009-0495-7. PMID 19551325. BCL2L10 human gene location in the UCSC Genome Browser. BCL2L10 ...
Excess progenitor cell proliferation that leads to gross brain abnormalities is often lethal, as seen in caspase-3 or caspase-9 ... Kuida, K (1998). "Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94: 325-337 ... to cells (such as feedback from neighbors, stress or DNA damage), mitochondria release caspase activators that trigger the cell ... Kroemer G, Martin SJ (2005). "Caspase-independent cell death". Nature Medicine. 11 (7): 725-30. doi:10.1038/nm1263. PMID ...
"Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9". Cell. 94 (3): 325-37. doi:10.1016/ ... 297 (5580): 365-9. Bibcode:2002Sci...297..365C. doi:10.1126/science.1074192. PMID 12130776.. ...
... antagonizes both the precursor and mature forms of Smac and caspase-9". J. Biol. Chem. 280 (1): 174-82. doi:10.1074/jbc. ... "Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function". Nat. Cell Biol. 6 (9): 849-60. doi: ... 6 (9): 791-806. doi:10.1101/gr.6.9.791. PMID 8889548. Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O (2000). " ... 9 (3): 99-106. doi:10.1093/dnares/9.3.99. PMID 12168954. Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, ...
In addition, several other molecules, most notably caspase-3, have been reported to co-purify with the apoptosome and caspase-3 ... Another targeted molecule for cancer therapy involves the caspase family and their regulators. The inhibition of caspase ... this initiator caspase can then activate effector caspases and trigger a cascade of events leading to apoptosis. The term ... "Caspase-8 and Apaf-1-independent caspase-9 activation in Sendai virus-infected cells". The Journal of Biological Chemistry. 277 ...
The Patched dependence receptor triggers apoptosis through a DRAL-caspase-9 complex. », Nat Cell. Biol, 2009 Furne et al., « ...
"Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity". Experimental Cell Research ... 61 (8): 3443-9. PMID 11309306. Weinmann AS, Bartley SM, Zhang T, Zhang MQ, Farnham PJ (October 2001). "Use of chromatin ... doi:10.1016/S0896-6273(02)00861-9. PMID 12372286. S2CID 10534933. Song H, Xia SL, Liao C, Li YL, Wang YF, Li TP, Zhao MJ ( ... doi:10.1016/S0896-6273(02)00861-9. PMID 12372286. S2CID 10534933. Kara NZ, Toker L, Agam G, Anderson GW, Belmaker RH, Einat H ( ...
Caspase 9 can then go on to activate caspase 3 and caspase 7, which are responsible for destroying the cell from within. One of ... The release of cytochrome-c from mitochondria to the cytosol, where it activates the caspase family of proteases is believed to ... The Cytochrome c Protein Apoptosis & Caspase 3 - PMAP The Proteolysis Map-animation Cytochrome+c at the US National Library of ... This release of cytochrome c in turn activates caspase 9, a cysteine protease. ...
It recognizes bacterial molecules and stimulates an immune reaction . NOD1 protein contains a caspase recruitment domain (CARD ... an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB". The Journal of Biological Chemistry. 274 (21): 14560-7. doi: ... "A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis". The Journal of ... enhances pro-interleukin-1beta processing through the interaction with pro-caspase-1". Biochemical and Biophysical Research ...
A follow-up study researched to determine if the caspases were involved in the apoptosis seen in the previous study as well as ... The study confirmed that there was cleavage of caspase-3, -8, and -9. All three of these cysteine proteases play an important ...
Activation of pro-caspase 8 initiates apoptosis via signaling from cell-surface death receptors such as Fas proteins and their ... Activation of pro-caspase 9 is dependent on mitochondrial signaling pathways which are regulated by the Bcl-2 family of ... This then activates pro-caspase 9 and results in apoptosis of the cells. Polymorphisms in genes have been shown to increase or ... 9 (1): 11. doi:10.1186/1741-7015-9-11. ISSN 1741-7015. PMC 3038966. PMID 21288330. Malek, Maryam; Nematbakhsh, Mehdi (2015-06- ...
Lee SH, Stehlik C, Reed JC (2001). "Cop, a caspase recruitment domain-containing protein and inhibitor of caspase-1 activation ... Inohara N, del Peso L, Koseki T, Chen S, Nunez G (Jun 1998). "RICK, a novel protein kinase containing a caspase recruitment ... The encoded protein contains a C-terminal caspase recruitment domain (CARD), and is a component of signaling complexes in both ... 1999). "Nod1, an Apaf-1-like activator of caspase-9 and nuclear factor-kappaB". J. Biol. Chem. 274 (21): 14560-7. doi:10.1074/ ...
It can also prevent the formation of Apaf-1 and Caspase 9 complex by acting directly upon Apaf-1 rather than Caspase 9, as ... Hu, Yuanming (February 21, 1998). "Bcl-XL interacts with Apaf-1 and inhibits Apaf-1-dependent caspase-9 activation". ... January 22, 1999). "Bax-induced Caspase Activation and Apoptosis via Cytochromec Release from Mitochondria Is Inhibitable by ... which leads to caspase activation and ultimately, programmed cell death. It is a well-established concept in the field of ...
Apoptotic death from NGF withdrawal also requires caspase activity. Upon NGF withdrawal, caspase-3 activation occurs through an ... Once caspase-9 is activated, it can cleave and activate caspase-3 resulting in cell death. Notably, apoptosis does not release ... Cytochrome c promotes the activation of caspase-9 through the formation of the apoptosome. ... 9: 581. doi:10.3389/fneur.2018.00581. PMC 6056664. PMID 30065697. Ma S, Dielschneider RF, Henson ES, Xiao W, Choquette TR, ...
2006). "Overexpression of HAX-1 protects cardiac myocytes from apoptosis through caspase-9 inhibition". Circ. Res. 99 (4): 415- ... 9: e55279. doi:10.7554/eLife.55279. ISSN 2050-084X. PMC 7343390. PMID 32573439. Modem S, Reddy TR (2007). "An anti-apoptotic ...
This leads to the activation of caspases-3, -8, and -9. When these T lymphocytes were pretreated with caspase inhibitors, DNA ... This suggests that apoptosis that is triggered by zinc deficiency is dependent on caspase proteins. Similar results were shown ... the same study found that TPEN increased the expression of pro-apoptotic genes and led to the activation of caspase-11, a ... 583 (9): 1516-1520. doi:10.1016/j.febslet.2009.04.008. PMID 19364507. Zhang, Feng; Ma, Xue-Ling; Wang, Yu-Xiang; He, Cong-Cong ...
Rho inhibition induces caspase-9 and caspase-3-dependent apoptosis of cultured human endothelial cells. These proteins are ... Fesik SW, Shi Y (2001). "Controlling the caspases". Science. 294 (5546): 1477-1478. doi:10.1126/science.1062236. PMID 11711663 ... activates caspase-9 and caspase-3, leading to apoptosis. Although Zamzami et al. suggest that the release of cytochrome c is ... the caspases. Depending on their function, once activated, Bcl-2 proteins either promote the release of these factors, or keep ...
... activating caspase-9 and eventually inducing apoptosis via caspase-3 activation. Hsp70 inhibits this process by blocking the ... It does not bind directly to the procaspase-9 binding site, but likely induces a conformational change that renders procaspase- ... 9 binding less favorable. Hsp70 is shown to interact with Endoplasmic reticulum stress sensor protein IRE1alpha thereby ... "Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome". Nature Cell ...
2005). "Caspase-dependent and independent activation of acid sphingomyelinase signaling". J. Biol. Chem. 280 (28): 26425-26434 ... 2004). "Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation". Cell Death Differ. 11 ... 9 (2): 139-150. doi:10.1038/nrm2329. PMID 18216770. Hait, N. C.; Oskeritzian, C. A.; Paugh, S. W.; Milstien, S.; Spiegel, S. ( ... 4 (2): 212-9. doi:10.1016/0955-0674(92)90035-B. PMID 1318060. Nishizuka, Y. (1995). "Protein kinase C and lipid signaling for ...
... to inhibit their caspase-binding activity and allow for caspase activation of apoptosis. SMAC is ubiquitously expressed in many ... Du C, Fang M, Li Y, Li L, Wang X (2000). "Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation ... Huang Y, Park YC, Rich RL, Segal D, Myszka DG, Wu H (2001). "Structural basis of caspase inhibition by XIAP: differential roles ... DIABLO is also referred to as second mitochondria-derived activator of caspases or SMAC. This protein binds inhibitor of ...
2001). Isolation and Assay of Caspases. Ch. 1. Methods in Cell Biol. 66:1-27. Profile page at IISER Thiruvananthapuram Faculty ... 2001). A conserved XIAP-interaction motif in caspase-9 and Smac/Diablo regulates caspase activity and apoptosis. Nature. 410: ... Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade. Cell, 91(4), 479 ... "Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade". Cell. 91 (4): ...
Caspase-3, caspase-8, and caspase-9 have been reported to be modified by O-GlcNAc. Caspase-8 is modified near its cleavage/ ... Hyper-O-GlcNAcylation in PDAC cells appeared to be anti-apoptotic, inhibiting cleavage and activation of caspase-3 and caspase- ... deoxy-GlcNAc Reveals O-GlcNAc Modification of the Apoptotic Caspases That Can Block the Cleavage/Activation of Caspase-8". ... GlcNAc with 5S-GlcNAc accelerated caspase activation while pharmacological raising of O-GlcNAc with thiamet-G inhibited caspase ...
CASP16P: encoding protein Caspase 16, pseudogene. *CCDC113: encoding protein Coiled-coil domain-containing protein 113 ...
... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[30 ... BDNF was first isolated from pig brain in 1982 by Yves-Alain Barde and Hans Thoenen.[9] ... 9: 698. doi:10.3389/fneur.2018.00698. ISSN 1664-2295. PMC 6117390. PMID 30197620.. ...
The resulting deconstruction of cellular components is primarily carried out by specialized proteases known as caspases, but ... 268 (5210): 533-9. doi:10.1126/science.7725097. PMID 7725097.. *^ a b c d e f g h i j Dong Y, Zhang S, Wu Z, Li X, Wang WL, Zhu ... 272 (40): 25200-9. doi:10.1074/jbc.272.40.25200. PMID 9312134.. *^ a b Padmanabhan A, Vuong SA, Hochstrasser M (March 2016). " ... doi:10.1016/0014-5793(96)00920-9. PMID 8925925.. *^ a b Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD ...
HR has some similarities to animal pyroptosis, such as a requirement of caspase-1-like proteolytic activity of VPEγ, a cysteine ... November 2004). "VPEgamma exhibits a caspase-like activity that contributes to defense against pathogens". Current Biology. 14 ... 9 (6): 418-28. doi:10.1038/nri2566. PMC 4535331. PMID 19461672.. *^ a b c d Doan T (2008). Immunology. Lippincott Williams & ... doi:10.1016/S0962-8924(01)02004-9. PMID 11413042.. *^ a b Cerenius L, Kawabata S, Lee BL, Nonaka M, Söderhäll K (October 2010 ...
Nevertheless, TRADD binds FADD, which then recruits the cysteine protease caspase-8. A high concentration of caspase-8 induces ... On the other hand, activated caspases cleave several components of the NF-κB pathway, including RIP, IKK, and the subunits of ... 9: 444. doi:10.3389/fimmu.2018.00444. PMC 5857565. PMID 29593717.. *^ Korneev, KV; Atretkhany, KN; Drutskaya, MS; Grivennikov, ... 178 (9): 5701-5709. doi:10.4049/jimmunol.178.9.5701.. *^ Walsh LJ, Trinchieri G, Waldorf HA, Whitaker D, Murphy GF (May 1991). ...
"Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration". primary. The EMBO Journal. 22 (24 ... 18 (1): 131-9. doi:10.3233/JAD-2009-1134. PMID 19625751.. *^ a b c d e Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, ... doi:10.1016/S0006-291X(02)00498-9. PMID 12051730.. *^ a b c Sadri-Vakili G, Bouzou B, Benn CL, Kim MO, Chawla P, Overland RP, ... 14 (9): 1171-82. doi:10.1093/hmg/ddi130. PMID 15772088.. *^ a b Riessland M, Ackermann B, Förster A, Jakubik M, Hauke J, Garbes ...
... condensed apoptotic nuclei and a 2-4 fold increase in cortical precursors that stained immunopositive for cleaved caspase-3.[27 ... 17 (9): 2959-66. PMID 9096132.. *^ Gorski JA, Zeiler SR, Tamowski S, Jones KR (July 2003). "Brain-derived neurotrophic factor ... 9] In the brain, it is active in the hippocampus, cortex, and basal forebrain-areas vital to learning, memory, and higher ...
Angiotensinogen · Caspase · F12 · Kimotripsinogen · Pepsinogen · Proelastase · Prokarboksipolipeptidase · Prolipase · ... Trombin) · .22 · .23 · .24 (.1 ALA · .7 MMP-1 · .17 MMP-3/MMP-6 · .19 BMP-1 · .23 MMP-7 · .24 MMP-2/MMP-5 · .35 MMP-9 · ... 16 · .17 (.1 CPA · .2 CPB · .3 CPN · .4 CPS · .6 ACP · .9 CPS · .21 PSMA) · .18 ... 3 HSD · .4 · .5 · .6 · .7 · .8 · .9 · .10 · .11 · .12 · .13 · .14 · .15 · .16 · .17 · .18 · .19 · .20 · .21 · .22 · .23 · .24 · ...
"Crocetin prevents retinal degeneration induced by oxidative and endoplasmic reticulum stresses via inhibition of caspase ... InChI=1S/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+, ... InChI=1/C20H24O4/c1-15(11-7-13-17(3)19(21)22)9-5-6-10-16(2)12-8-14-18(4)20(23)24/h5-14H,1-4H3,(H,21,22)(H,23,24)/b6-5+,11-7+,12 ... 9] Transcrocetinate sodium was one of the first such compounds discovered.[8][10] ...
"A novel form of DAP5 protein accumulates in apoptotic cells as a result of caspase cleavage and internal ribosome entry site- ... 272 (2): 1101-9. doi:10.1074/jbc.272.2.1101. PMID 8995409.. *^ Méthot N, Song MS, Sonenberg N (October 1996). "A region rich in ... 276 (9): 6817-24. doi:10.1074/jbc.M007372200. PMID 11102443.. *. Lin L, Holbro T, Alonso G, Gerosa D, Burger MM (2001). " ...
Non obstante, a TRADD únese a FADD, o cal despois recruta a cisteína protease caspase-8. Unha alta concentración de caspase-8 ... Por outra parte, as caspases activadas clivan varios compoñentes da vía NF-κB, incluíndo a RIP, IKK, e as propias subunidades ... Med. 16 (4): 452-9. PMID 20208540. doi:10.1038/nm.2106.. *↑ Starkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK. ... U.S.A. 72 (9): 3666-70. Bibcode:1975PNAS...72.3666C. PMC 433057. PMID 1103152. doi:10.1073/pnas.72.9.3666.. ...
It is an energy dependent process mediated by proteolytic enzymes called caspases, which trigger cell death through the ... 9] In the average adult between 50 and 70 billion cells die each day due to apoptosis. Inhibition of apoptosis can result in a ...
Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7). Once initiator caspases are activated, they produce a chain reaction ... Caspase-1, Caspase-4, Caspase-5 and Caspase-11 are considered 'Inflammatory Caspases'.[7] ... Caspase-1, Caspase-4 and Caspase-5 in humans, and Caspase-1 and Caspase-11 in mice play important roles in inducing cell death ... or direct activation of Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) to degrade cellular components as shown in ...
"Caspase 8 small interfering RNA prevents acute liver failure in mice". Proc Natl Acad Sci USA 100 (13): 7797-802. PMC 164667 ... "Proc Natl Acad Sci USA 103 (48): 18054-9. PMC 1838705. PMID 17110445. doi:10.1073/pnas.0605389103.. ... "Nucleic Acids Res 32 (Web Server issue): W124-9. PMC 441580. PMID 15215364. doi:10.1093/nar/gkh442.. ... doi:10.1016/0092-8674(95)90082-9.. *↑ Pal-Bhadra M, Bhadra U, Birchler J (1997). "Cosuppression in Drosophila: gene silencing ...
a b Nikolaev A. APP Binds DR6 to Cause Axon Pruning and Neuron Death via Distinct Caspases. Nature. 19. februar 2009;457(7232): ... doi:10.1016/S0197-4580(98)00052-9. PMID 9661992. *^ a b c d Impact économique de la démence (English: The Economical Impact of ... 1994;90(9):417-23. PMID 7967534. *^ Sundowning and Circadian Rhythms in Alzheimer's Disease. The American Journal of Psychiatry ... 2003;64 Suppl 9:7-10. PMID 12934968. *^ Amyloid Deposition as the Central Event in the Aetiology of Alzheimer's Disease. Trends ...
Ubiquitin ligases transfer ubiquitin to its pendant, proteins, and caspases, which engage in proteolysis in the apoptotic cycle ... doi:10.1016/S0014-5793(99)01122-9. PMID 10518936.. *^ Betts, M.J.; R.B. Russell (2003). "Hydrophobic amino acids". Amino Acid ... 61 (8-9). ISSN 0214-6282.. *^ Sekhar, Rajagopal V; Patel, Sanjeet G (2011). "Deficient synthesis of glutathione underlies ... doi:10.1016/S0014-5793(99)01122-9. PMID 10518936.. *952-10-3056-9 Interaction of alcohol and smoking in the pathogenesis of ...
... caspase-8 and caspase-10. In some types of cells (type I), processed caspase-8 directly activates other members of the caspase ... Caspase-independent apoptosis[edit]. The characterization of the caspases allowed the development of caspase inhibitors, which ... Caspases. Caspases play the central role in the transduction of ER apoptotic signals. Caspases are proteins that are highly ... There are two types of caspases: initiator caspases, caspase 2,8,9,10,11,12, and effector caspases, caspase 3,6,7. The ...
Caspase. *Caspase 1. *Caspase 2. *Caspase 3. *Caspase 4. *Caspase 5. *Caspase 6 ... 383 (7-8): 1285-9. doi:10.1515/BC.2002.144. PMID 12437118.. *. Wex T, Bühling F, Wex H, et al. (2001). "Human cathepsin W, a ...
Also, it is extensively used in research for the detection of DNA damage,[34][35] caspase cleavage and apoptosis.[36] In ... Apoptosis (quantification, measurement of DNA degradation, mitochondrial membrane potential, permeability changes, caspase ...
Barr · 0-9 · A B C D E F G H I J K L M N O P Q R S T U V W X Y Z ...
"Newcastle disease virus exerts oncolysis by both intrinsic and extrinsic caspase-dependent pathways of cell death". Journal of ... 9] by researchers who had isolated the strain in 1968.[10][11] It appears the virus preferentially targets and replicates in ...
Diaz F, Bourguignon LY (2000). «Selective down-regulation of IP(3)receptor subtypes by caspases and calpain during TNF alpha - ... 14 (9): 1711-8. PMC 515316. . PMID 15342556. doi:10.1101/gr.2435604. !CS1 manut: Uso explícito de et al. (link) !CS1 manut: ... 2 (1): 9-22. PMID 8081734. !CS1 manut: Uso explícito de et al. (link) !CS1 manut: Nomes múltiplos: lista de autores (link) ...
... binds to the death receptors DR4 (TRAIL-RI) and DR5 (TRAIL-RII). The process of apoptosis is caspase-8-dependent. Caspase ... activates downstream effector caspases including procaspase-3, -6, and -7, leading to activation of specific kinases.[11] TRAIL ... "Differential cleavage of Mst1 by caspase-7/-3 is responsible for TRAIL-induced activation of the MAPK superfamily". Cellular ...
Ubiquitin ligases transfer ubiquitin to its pendant, proteins, and caspases, which engage in proteolysis in the apoptotic cycle ... doi:10.1016/S0014-5793(99)01122-9. PMID 10518936.. *^ Betts, M.J.; R.B. Russell (2003). "Hydrophobic amino acids". Amino Acid ... 61 (8-9). ISSN 0214-6282.. *^ Lill R, Mühlenhoff U (2006). "Iron-sulfur protein biogenesis in eukaryotes: components and ... doi:10.1016/S0014-5793(99)01122-9. PMID 10518936.. *952-10-3056-9 Interaction of alcohol and smoking in the pathogenesis of ...
... accompanied by activations of nuclear factor kappaB and caspase-3.. „Life Sci". 77 (7), s. 824-836, 2005-07-01. PMID: 15936354. ... EFSA Journal". 998, s. 1-9, 2009. *↑ a b c d Johannes Westendorf: Noni (Morinda citrifolia). Old Tradition and Modern ... Krzew osiągający wysokość do 9 metrów.. Liście. Duże, błyszczące, głęboko unerwione, o gładkich brzegach.. Owoce. Zebrane w ... Wartość energetyczna pulpy wynosi około 136 kJ/100 g[9]. Głównymi mikronutrientami są witamina C, niacyna (witamina B3), żelazo ...
Alignment of the seven Drosophila caspases colored by motifs as identified by MEME. When motif positions and sequence ... In standard profile analysis, the matrix includes entries for each possible character as well as entries for gaps.[9] ... This corrects for non-random selection of the sequences given to the alignment program.[9] ... 9] PRRP performs best when refining an alignment previously constructed by a faster method.[9] ...
To protect your privacy, your account will be locked after 6 failed attempts. After that, you will need to contact Customer Service to unlock your account.. You have 4 remaining attempts.. You have 3 remaining attempts.. You have 2 remaining attempts.. You have 1 remaining attempt.. Contact Customer Service ...
Ab12490 Caspase 3 siRNA vector ?ab12496 Caspase 8 siRNA vector ?ab12504 Caspase 9 siRNA vector ... I have now added the western blot image for the caspase 3 knockdown. It can be viewed on www.abcam.com/ab12490. If you do have ... Im interesting in your siRNA vectars against several caspases but there are no datas on your web pages. Could you show me the ... between the sense portion of the siRNA sequence and the mRNA enables the nuclease enzyme to bind and cleave the caspase ...
Caspase 9 is responsible for initiating the caspase activation cascade during apoptosis. Apoptosis is a physiological mechanism ... of homeostasis and development, and caspases are the ex ... EC 3.4.22.-/Caspase 9 From MEDLINE®/PubMed®, a database of the ... Caspase 9 / metabolism*. Epidermis / enzymology*, pathology. Female. Humans. Immunohistochemistry / methods. Male. Middle Aged ... Counts of caspase 9 positive cells from the epidermis of psoriatic skin lesions were significantly lower than those seen in ...
Anti-Caspase-9 antibody (ab52298) has been cited in 22 publications. References for Human, Mouse, Rat in ICC/IF, IHC, IHC-Fr, ...
Within caspase-9s active site, in order for catalytic activity to occur there has to be specific amino acids in the right ... Caspase 8, NLRP1, and XIAP. The Proteolysis Map Caspase Caspase-3 Apoptosome Apaf-1 GRCh38: Ensembl release 89: ENSG00000132906 ... Similar to other caspases, caspase-9 has three domains: N-terminal pro-domain, large subunit, and a small subunit. The N- ... The introduction of caspases may also have medical benefits. In the context of graft versus host disease, caspase-9 can be ...
Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK.. Allan LA1, Morrice N, Brady S, Magee G, Pathak S, ... an initiator protease that activates caspase-3 and downstream caspases to initiate cellular destruction. However, survival ... Here, we show that the ERK MAPK pathway inhibits caspase-9 activity by direct phosphorylation. In mammalian cell extracts, ... We suggest that phosphorylation and inhibition of caspase-9 by ERK promotes cell survival during development and tissue ...
... derived caspase substrates are widely used for the colorimetric detection of various caspase activities. Cleavage of pNA ... pNA has maximum absorption around 408 nm.; Caspase-9 substrate; Ac-LEHD-pNA; Ac-Leu-Glu-His-Asp-pNA ... peptides by caspases generates pNA that is monitored colorimetrically at ~405 nm. ... pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. ...
The human caspase-3, caspase-4, wild type, and mutant (C287S) caspase-9 cDNAs were cloned into the BamHI and XhoI sites of a ... including caspase-4, caspase-8, caspase-9, and nematode CED-3 in mammalian cells. The interaction with caspase-9 was mediated ... the relevance of the interaction between Apaf-1 and caspase-4 or caspase-8 is unclear. In contrast to caspase-9, Apaf-1 did not ... Lower) The expression of caspase-3 and -4 (B), caspase-9 (C), and CED-3 and Apaf-1 proteins (D). Reduced level of pro-caspase-9 ...
Human Caspase 9, Synthetic Peptide, Invitrogen 50µg Life Sciences:Protein Biology:Proteins:Peptides:Catalog Peptides ... 1 leads to activation of the protease which then cleaves and activates caspase-3. Caspase 9 promotes DNA damage-induced ... In humans, dysfunctional Caspase 9 expression vary from tissue to tissue. Low levels of Caspase 9 may play a role in cancer ... Caspase 9 is active as a heterotetramer, is present in the cytosol and, upon activation, translocates to the mitochondria. ...
What is caspase 9? Meaning of caspase 9 medical term. What does caspase 9 mean? ... Looking for online definition of caspase 9 in the Medical Dictionary? caspase 9 explanation free. ... The influence of compounds 2-4 on caspase 3/7, caspase 8 and caspase 9 activity in CCRF-CEM leukemia cells was detected using ... The influence of compound 3 on caspase 3/7, caspase 8 and caspase 9 activity in CCRF-CEM leukemia cells was detected using ...
Rabbit Polyclonal Anti-Caspase-9 Antibody cited in 15 publications. Validated: WB, Flow-IC, IHC, IHC-Fr, IHC-P, IP. Tested ... Initiator caspases (such as Caspase-9) sense and respond to various signals i... Read full blog post.. ... Caspase 3, the executioner of apoptosis. Caspase-3 enzyme is a member of the family of endoproteases which regulate ... Caspase-3 is known as an executioner caspase in apoptosis because of its role in coordinating the destruction of cellular stru ...
Phospho-Caspase 9 (Thr125) Polyclonal Antibody from Invitrogen for Western Blot and Immunohistochemistry (Paraffin) ... 1 leads to activation of the protease which then cleaves and activates caspase-3. Caspase 9 promotes DNA damage-induced ... In humans, dysfunctional Caspase 9 expression vary from tissue to tissue. Low levels of Caspase 9 may play a role in cancer ... Cite Phospho-Caspase 9 (Thr125) Polyclonal Antibody. The following antibody was used in this experiment: Phospho-Caspase 9 ( ...
Order monoclonal and polyclonal Caspase 9 antibodies for many applications. Selected quality suppliers for anti-Caspase 9 ... caspase-8 (show CASP8 Antibodies) and caspase-9 contribute to the cyclic stretch-induced apoptosis, but functioned differently ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... anti-Caspase 8, Apoptosis-Related Cysteine Peptidase Antibodies * anti-Caspase 7, Apoptosis-Related Cysteine Peptidase ...
BioVision develops and offers a wide variety of products including assay kits, antibodies, recombinant proteins & enzymes, and other innovative research tools for studying Apoptosis, Metabolism, Cell Proliferation, Cellular Stress, Cell Damage and Repair, Diabetes, Obesity and Metabolic Syndrome, Stem Cell Biology, Gene Regulation, Signal Transduction, etc. BioVisions products are currently being sold in more than 60 countries worldwide.
... but possibly not the executioners caspase-3 and caspase-7, are required for primitive erythropoiesis in the early embryo. These ... Caspase-9 has a nonapoptotic function in Xenopus embryonic primitive blood formation.. [Hong Thi Tran, Mathias Fransen, ... Caspases constitute a family of cysteine proteases centrally involved in programmed cell death, which is an integral part of ... However, it has become clear that specific caspases also have functions independent of cell death. In order to identify novel ...
Apaf-3 was identified as a member of the caspase family, caspase-9. Caspase-9 and Apaf-1 bind to each other via their ... Activated caspase-9 in turn cleaves and activates caspase-3. Depletion of caspase-9 from S-100 extracts diminished caspase-3 ... Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.. Li P1, Nijhawan ... We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. ...
1B) (4), implying a defect at or upstream of this caspase. Ras extracts, however, were not resistant to caspase activation ... Caspases are intracellular proteases that function as initiators and effectors of apoptosis. The kinase Akt and p21-Ras, an Akt ... Regulation of Cell Death Protease Caspase-9 by Phosphorylation. By Michael H. Cardone, Natalie Roy, Henning R. Stennicke, Guy S ... Regulation of Cell Death Protease Caspase-9 by Phosphorylation. By Michael H. Cardone, Natalie Roy, Henning R. Stennicke, Guy S ...
... triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase ... Western Blot: Caspase 9 Antibody Cowan et al employed the Caspase 9 antibody to classify in vivo activation of caspases 9 and 3 ... Activated caspase 9 primary signaling occurs through caspase 3, which it cleaves and activates. The Caspase 9 antibody was used ... Among the subclass of initiator caspases that include subtypes -2, -8 and -9, caspase 9 is expressed in a variety of human ...
Compare and order Caspase 9 ELISA Kits. View citations, images, detection ranges, sensitivity, prices and more. Recommended ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... This protein is processed by caspase APAF1\; this step is thought to be one of the earliest in the caspase activation cascade. ... Search Caspase 9 ELISA Kits for other reactivities: Guinea Pig,. Pig (Porcine),. Cow (Bovine),. Goat,. Dog (Canine),. Chicken, ...
Caspase-9 Substrate LEHD-pNA. Provided in the ready-to-use form ...
Caspase 9 Substrate LEHD is available 4 times from supplier Biovision at Gentaur.com shop ... Caspase 9 Substrate LEHD. Caspase 9 Substrate LEHD is available 4 times from Biovision labs 1075-200 , Caspase-9 Substrate LEHD ... Description Human and some mouse caspases are active in apoptosis and cell death and even in necrosis and inflammation. CASP ... 1075-1000 , Caspase-9 Substrate LEHD-AFC size: 1000 assays , 701.83 USD ...
... and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein (XIAP) against recombinant caspase-9 ... Inhibitor specificity of recombinant and endogenous caspase-9. Ciara A. RYAN, Henning R. STENNICKE, Victor E. NAVA, Jennifer B. ... Inhibitor specificity of recombinant and endogenous caspase-9. Ciara A. RYAN, Henning R. STENNICKE, Victor E. NAVA, Jennifer B. ... Inhibitor specificity of recombinant and endogenous caspase-9 Message Subject (Your Name) has forwarded a page to you from ...
Anti-CD19 CAR-T Cells With Inducible Caspase 9 Safety Switch for B-cell Lymphoma. The safety and scientific validity of this ... AP1903 (0.4 mg/kg), a dimerizing agent to engage and activate the caspase 9 safety switch to trigger iC9-CAR19 T cell death by ... A Phase I Study of Autologous Activated T-cells Targeting the CD19 Antigen and Containing the Inducible Caspase 9 Safety Switch ... a dimerizing agent that is designed to engage and activate the caspase 9 safety switch to trigger iC9-CAR19 T cell death by ...
D609 stimulated FasL-induced cell death in caspase-8-deficient Jurkat cells, indicating that D609 acts downstream of caspase-8 ... a broad-spectrum caspase inhibitor, indicating that FasL can activate both caspase-dependent and -independent cell death ... D609 enhanced caspase-independent ceramide increase and cell death in response to FasL. Also, D609 overcame zVAD-fmk-conferred ... FasL-induced caspase activation was abolished by zVAD-fmk, whereas ceramide production was only partially impaired. ...
NMR Structure of an Antagonists of the XIAP-Caspase-9 Interaction Complexed to the BIR3 domain of XIAP. *DOI: 10.2210/pdb1TFT/ ... results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. ...
Intrigued by the multiple ways to control caspase-9s activity, we sought after designing synthetic caspase-9 inhibitors in ... All in all, the regulation of caspase-9 occurs on a variety of levels that requires almost every surface of the enzyme. Through ... We report the first stabilized α-helical peptides that harness the native regulatory mechanism of caspase-9 and the BIR3 domain ... Furthermore, an interaction was discovered between CARD and the catalytic core of caspase-9 in the presence of a properly ...
Anti-Caspase 3 Antibody, active (cleaved) form, Anti-Caspase 3 Antibody, active (cleaved) form detects level of Caspase 3 and ... Sevoflurane postconditioning prevents activation of caspase 3 and 9 through antiapoptotic signaling after myocardial ischemia- ...
... an inhibitor of caspase-3, caspase-6, caspase-7, and caspase-10, from Santa Cruz. Purity: ≥90% (solid) ... and irreversible inhibitor of caspase-3, caspase-6, caspase-7, caspase-8 and caspase-10. Caspase inhibitors play an important ... Caspase-3 InhibitorAn inhibitor of caspase-3, caspase-6, caspase-7, and caspase-10. *Home. ... Application: An inhibitor of caspase-3, caspase-6, caspase-7, and caspase-10 ...
Rabbit Polyclonal Caspase 9 (cleaved Asp330) antibody. Validated in WB, IHC-P. Tested in Human. - professional antibody ... Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive ... APAF3,CASP9,ICELAP6,MCH6,PPP1R56,caspase 9,Caspase 9 Background This gene encodes a member of the cysteine-aspartic acid ... Caspase 9 (cleaved Asp330) antibody detects endogenous levels of fragment of activated Caspase 9 resulting from cleavage ...
Casp9 (mouse)(Casp9, caspase 9, apoptosis-related cysteine peptidase) can be used for N/A. ... Recombinant Mouse Caspase 9. Download Datasheet See All Casp9 Products. Bring this labeled protein directly to your bench! ... Caspases and Regulators Proteins CASP9 HAX1 CASP6 CASP4 BIRC7 CASP1 COL4A3 PYCARD NOD1 ... Casp9 caspase 9 [ Mus musculus ]. Synonyms:. caspase 9; Mch6; AI115399; AW493809; ICE-LAP6; Caspase-9; Casp9; caspase-9; ...
  • Akt acts as an allosteric inhibitor of caspase-9 because the site of phosphorylation of serine-196 is far from the catalytic site. (wikipedia.org)
  • The inhibitor affects the dimerization of caspase-9 and causes a conformational change that affects the substrate-binding cleft of caspase-9. (wikipedia.org)
  • The inhibitory potency of acetyl-Asp-Glu-Val-Asp-aldehyde ('Ac-DEVD-CHO'), benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone ('Z-VAD-FMK') and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein ('XIAP') against recombinant caspase-9 were predictive of the efficacy of these compounds in a cell-free system. (biochemj.org)
  • These results consolidate previous findings that CrmA is a potent inhibitor of caspase-9 in vitro , yet fails to block caspase-9-mediated cell death. (biochemj.org)
  • At high FasL concentration (500 ng/mL), cell death was significantly, but not completely, inhibited by zVAD-fmk, a broad-spectrum caspase inhibitor, indicating that FasL can activate both caspase-dependent and -independent cell death signaling pathways. (mdpi.com)
  • Caspase-3 inhibitor (Z-DEVD-FMK ) is a cell-permeable, potent, and irreversible inhibitor of caspase-3, caspase-6, caspase-7, caspase-8 and caspase-10. (scbt.com)
  • See how others have used Caspase-3 Inhibitor. (scbt.com)
  • The broad spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone failed to block the depolarization of mitochondrial membranes induced by resveratrol, further indicating that resveratrol action was independent of upstream caspase-8 activation via receptor ligation. (aacrjournals.org)
  • In these experiments, the caspase activation pathways during receptor and chemical-mediated apoptosis were investigated using the broad spectrum caspase inhibitor Z-VAD-FMK. (aacrjournals.org)
  • This conclusion is supported by the observation that in HL-60/Apaf-1 cells, ectopic expression of dominant negative caspase-9, its inhibitory short isoform caspase-9b, or XIAP or treatment with the caspase inhibitor zVAD (50μ m ) inhibited Apaf-1-induced caspase-8 and Bid cleavage, mitochondrial ΔΨm, release of cyt c , and apoptosis. (aacrjournals.org)
  • In contrast, a transient transfection of dominant negative caspase-8 or CrmA or exposure to caspase-8 inhibitor zIETD-fmk inhibited the processing of procaspase-8 and Bid but did not inhibit the cytosolic accumulation of cyt c in either the untreated HL-60/Apaf-1 cells or the etoposide-treated HL-60/Apaf-1 and HL-60/neo cells. (aacrjournals.org)
  • Here, we made unexpected observations that the caspase-9 inhibitor (C9i) enhanced apoptosis in response to selected stimuli, and HEp-2 cells which were made deficient in caspase-9 using siRNA exhibited no resistance to apoptotic signals and actually demonstrated increased apoptotic sensitivity to oridonin. (spandidos-publications.com)
  • Therefore, in the present study, a siRNA targeting p38 MAPK (siRNA-p38 MAPK) and the caspase‑9 specific inhibitor z-LEHD-fmk were used to examine the crosstalk between p38 MAPK and caspase-9 during mitochondria-mediated apoptosis in the TαPcZn-PDT‑treated LoVo cells. (spandidos-publications.com)
  • Protein Kinase C Inhibitor and Irradiation-induced Apoptosis: Relevance of the Cytochrome c-mediated Caspase-9 Death Pathway -- Rocha et al. (aacrjournals.org)
  • The Caspase-9 Inhibitor III, also referenced under CAS 403848-57-7, controls the biological activity of Caspase-9. (merckmillipore.com)
  • A potent, irreversible inhibitor of caspase-9. (merckmillipore.com)
  • Once inside the cell, the inhibitor binds covalently to the active caspase (10). (celltechnology.com)
  • Cells were seeded in RPMI 1640 medium + 10% FBS with pretreatment with NAC, inhibitors of caspase-9 and -3 or a pan-caspase inhibitor, and then were exposed to 100 μM of emodin for 24 h. (nih.gov)
  • In order to evaluate the roles of caspase-mediated pathways in emodin-induced apoptotic death of WEHI-3 cells, cells were pretreated with a pan-caspase inhibitor (Z-VAD-FMK), and then exposed to emodin. (nih.gov)
  • MIHA is an inhibitor of apoptosis protein (IAP) that can inhibit cell death by direct interaction with caspases, the effector proteases of apoptosis. (rupress.org)
  • Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9. (nih.gov)
  • Z-LEHD-FMK Irreversible Caspase-9 inhibitor. (apexbt.com)
  • The caspase 9 inhibitor Z-LEHD-FMK protects human liver cells while permitting death of cancer cells exposed to tumor necrosis factor-related apoptosis-inducing ligand. (apexbt.com)
  • Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury. (apexbt.com)
  • Z-LEHD-FMK is a specific and irreversible inhibitor of caspase-9 [1]. (apexbt.com)
  • Abcam's Caspase 9 Inhibitor Drug Detection Kit provides an effective means for screening caspase inhibitors using fluorometric methods. (abcam.cn)
  • Caspase activity (RFU) in presence of 0µM - 40µM of z-VAD-FMK (generic caspase inhibitor), assessed using LEHD-AFC as caspase 9 substrate and following Caspase 9 Inhibitor Drug Detection Kit ( ab102493 ) protocol. (abcam.cn)
  • Pathogenic relevance of active caspase-9 was shown by intranasal delivery of a novel cell membrane-penetrating highly specific inhibitor for active caspase-9 at 4 h postreperfusion (hpr). (elsevier.com)
  • Thus, ARC represents an inhibitor of apoptosis expressed in muscle that appears to selectively target caspases. (pnas.org)
  • Moreover, we show that, in contrast to the human enzymes, mouse caspase-7 is as efficient as caspase-3 at cleaving and thus inactivating ICAD (inhibitor of caspase-activated DNase), the inhibitor of apoptotic DNA fragmentation. (jneurosci.org)
  • Caspase substrate specificity has been widely used in caspase based inhibitor and drug design. (wikipedia.org)
  • Per usual in non-apoptotic growing cells caspase activated dnase is held in check inactivated in the cytoplasm thanks to the association with its inhibitor, inhibitor of caspase-activated DNase (ICAD) also known as DNA fragmentation factor 45 kDa (DFF45). (wikipedia.org)
  • Caspase-9 has a preferred cleavage sequence of Leu-Gly-His-Asp-(cut)-X. Negative regulation of caspase-9 occurs through phosphorylation. (wikipedia.org)
  • Cleavage of pNA peptides by caspases generates pNA that is monitored colorimetrically at ~405 nm. (anaspec.com)
  • Activation of downstream caspases through several stimuli leads to cleavage of target proteins and execution of the apoptotic program ( 13 ). (pnas.org)
  • Intermediate caspase-9 cleavage forms may also be seen at ~21 kDa. (novusbio.com)
  • Caspase 9 (Cleaved-Asp353) Antibody detects endogenous levels of fragment of activated Caspase 9 resulting from cleavage adjacent to Asp353. (genetex.com)
  • Activation of caspases during apoptosis results in the cleavage of critical cellular substrates so precipitating the dramatic morphological changes of apoptosis. (biovendor.com)
  • Apaf-1+/− MEFs) or Apaf-1−/− MEFs also induced the processing of procaspase-9 and procaspase-8, Bid cleavage, and apoptosis. (aacrjournals.org)
  • This triggers the mitochondrial ΔΨm and cyt c release into the cytosol through a predominant mechanism other than cleavage of caspase-8 and/or Bid. (aacrjournals.org)
  • Typhonium flagelliforme induces apoptosis in CEMss cells via activation of caspase-9, PARP cleavage and cytochrome c release: its activation coupled with G0/G1 phase cell cycle arrest. (semanticscholar.org)
  • article{Mohan2010TyphoniumFI, title={Typhonium flagelliforme induces apoptosis in CEMss cells via activation of caspase-9, PARP cleavage and cytochrome c release: its activation coupled with G0/G1 phase cell cycle arrest. (semanticscholar.org)
  • Caspases can be detected via immunoprecipitation, immuno-blotting techniques using caspase specific antibodies, or by employing fluorogenic substrates which become fluorescent upon cleavage by the caspase. (celltechnology.com)
  • The active form of caspase-9 is generated by cleavage of the pro-caspase-9 protein into fragments, known as the large and small fragments. (bio-rad-antibodies.com)
  • The trigger for caspase-9 cleavage is the formation of the apoptosome (comprising of cytochrome c, APAF-1, dATP and pro-caspase-9), upon stimulation of the intrinsic apoptosis pathway. (bio-rad-antibodies.com)
  • The antibody can therefore be used to distinguish the p10 caspase-9 fragment from other pro-caspase-9 cleavage products. (bio-rad-antibodies.com)
  • The late activation of caspase-8 and data showing the partial cleavage of pro-apoptotic protein BID suggest that the initial activation of caspase-9 may be potentiated by a feedback amplification loop involving the caspase-8/BID pathway. (oup.com)
  • Caspase-9 and related caspase activity can be quantified by spectrophotometric detection of free pNA (= 400 nm) after cleavage from the peptide substrate LEHD-pNA, using a spectrophotometer or multi-well plate reader. (antibody-antibodies.com)
  • Oxidant-induced neuronal apoptosis has been shown to involve potassium and zinc dysregulation, energetic dysfunction, activation of stress-related kinases, and caspase cleavage. (jneurosci.org)
  • Moreover, we found that activation of p38 is required for caspase 3 and 9 cleavage, suggesting that potassium currents enhancement is required for caspase activation. (jneurosci.org)
  • Based on these findings, we conclude that oxidation of sulfhydryl groups on intracellular targets results in intracellular zinc release, p38 phosphorylation, enhancement of potassium currents, caspase cleavage, energetic dysfunction, and translationally independent apoptotic cell death. (jneurosci.org)
  • Activation involves dimerization and often oligomerisation of pro-caspases, followed by cleavage into a small subunit and large subunit. (wikipedia.org)
  • Both arms impinge upon, and activate, procaspase 9 via two different cleavage sites within the procaspase 9 molecule (D330 and D315, respectively). (elsevier.com)
  • Activation of apical caspases, such as caspase-8, through cell death receptors or other apoptotic stimuli leads to activation of downstream caspases, precipitous cleavage of target proteins and execution of the apoptotic program ( 7 , 8 ). (pnas.org)
  • Apoptosis, or programmed cell death, is mediated by the activation of caspases (Casp), a family of cysteine proteases present as proenzymes in all cells and activated by cleavage and reorganization of their subunits after an intracellular or extracellular apoptotic signal ( Nicholson, 1999 ). (jneurosci.org)
  • We observed that caspase-9 dimerization resulted in the loss of mitochondrial membrane potential and the cleavage of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1. (houstonmethodist.org)
  • Moreover, cleavage-resistant Bcl-2, Bcl-xL, or Mcl-1 potently inhibited caspase-9-dependent loss of mitochondrial membrane potential and the release of cytochrome c. (houstonmethodist.org)
  • Our data suggest that a caspase-9 signaling cascade induces feedback disruption of the mitochondrion through cleavage of anti-apoptotic Bcl-2, Bcl-xL, and Mcl-1. (houstonmethodist.org)
  • It is the predominant caspase involved in the cleavage of amyloid-beta 4A precursor protein, which is associated with neuronal death in Alzheimer's disease. (wikipedia.org)
  • In vitro, caspase-3 has been found to prefer the peptide sequence DEVDG (Asp-Glu-Val-Asp-Gly) with cleavage occurring on the carboxy side of the second aspartic acid residue (between D and G). Caspase-3 is active over a broad pH range that is slightly higher (more basic) than many of the other executioner caspases. (wikipedia.org)
  • CAD release from ICAD inhibition is achieved by cleavage of ICAD at these Asp residues by the caspase-3. (wikipedia.org)
  • Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene. (wikipedia.org)
  • On www.antibodies-online.com are 474 Caspase 9, Apoptosis-Related Cysteine Peptidase (CASP9) Antibodies from 35 different suppliers available. (antibodies-online.com)
  • The kinase Akt and p21-Ras, an Akt activator, induced phosphorylation of pro-caspase-9 (pro-Casp9) in cells. (sciencemag.org)
  • Active Casp9 then directly cleaves to and activates pro-Casp3, initiating a cascade of additional caspase activation that culminates in apoptosis. (sciencemag.org)
  • The observed casp9 activity in the ventral blood island (VBI) turns out to be independent of the activity of the downstream effectors casp3 and caspase-7 (casp7). (biologists.org)
  • Caspase 9 antibody LS-C148251 is an unconjugated rabbit polyclonal antibody to human Caspase 9 (CASP9) (aa188-206). (lsbio.com)
  • LS-F1857 is a 96-well enzyme-linked immunosorbent assay (ELISA) for the Qualitative detection of Human CASP9 / Caspase 9 in samples of Adherent Cell Cultures. (lsbio.com)
  • The objective of this study was to investigate whether polymorphisms of caspase-9 (CASP9) gene and RUNX3 are associated with IBD susceptibility and clinical phenotypes. (ox.ac.uk)
  • This is done by a serine-threonine kinase, Akt, on serine-196 which inhibits the activation and protease activity of caspase-9, suppressing caspase-9 and further activation of apoptosis. (wikipedia.org)
  • Many pro-apoptotic signals activate caspase-9, an initiator protease that activates caspase-3 and downstream caspases to initiate cellular destruction. (nih.gov)
  • Recent studies indicate that Caenorhabditis elegans CED-4 interacts with and promotes the activation of the death protease CED-3, and that this activation is inhibited by CED-9. (pnas.org)
  • Furthermore, CED-4 promotes the activation of the death protease CED-3, and this activation is inhibited by CED-9 ( 10 - 12 ). (pnas.org)
  • In the presence of dATP and cytochrome c , a molecule that is released from mitochondria during apoptosis, Apaf-1 binds to caspase-9 and induces the activation of caspase-3, a downstream death protease ( 20 ). (pnas.org)
  • Caspase 9 (ICE-like apoptotic protease 6, ICE LAP6, apoptotic protease Mch6, apoptotic protease activating factor 3, Apaf3) is a member of the peptidase family C14 that contains a CARD domain. (fishersci.com)
  • Binding of caspase-9 to Apaf- 1 leads to activation of the protease which then cleaves and activates caspase-3. (fishersci.com)
  • Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. (nih.gov)
  • Mutation of the active site of caspase-9 attenuated the activation of caspase-3 and cellular apoptotic response in vivo, indicating that caspase-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP. (nih.gov)
  • Ras extracts, however, were not resistant to caspase activation induced by granzyme B (GraB) ( 5 ), which implies that other routes of protease activation were intact ( Fig. 1 D). (sciencemag.org)
  • Cell death via apoptosis is a key cellular function triggered by the cell death receptor family and their ligands which signal through downstream adaptor molecules and the caspase protease family. (novusbio.com)
  • This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. (genetex.com)
  • The aspartic acid specific protease caspase-9 has been linked to the mitochondrial death pathway. (creativebiomart.net)
  • caspase-9 thus is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP. (biovendor.com)
  • In a model system of mature B cells, differences in caspase-3 processing have suggested that antigen receptor (BCR)-mediated apoptosis may involve a zVAD-insensitive initiator protease(s). (nih.gov)
  • Rabbit anti caspase-9 p10 antibody recognizes caspase-9, a member of the cysteine-aspartic acid protease family. (bio-rad-antibodies.com)
  • Programmed cell death (Apoptosis) and cytokine secretion, which are mediated by activation of different caspase-family protease cascades, are examples of the numerous mechanisms of our innate immunity against viral infections. (escholarship.org)
  • Caspases ( c ysteine- asp artic prote ases , c ysteine asp art ases or c ysteine-dependent asp artate-directed prote ases ) are a family of protease enzymes playing essential roles in programmed cell death (including apoptosis , pyroptosis and necroptosis ) and inflammation . (wikipedia.org)
  • They are named caspases due to their specific cysteine protease activity - a cysteine in its active site nucleophilically attacks and cleaves a target protein only after an aspartic acid residue. (wikipedia.org)
  • In the nematode C. elegans , activation of the cell death protease CED-3 is positively regulated by CED-4 and inhibited by CED-9 through direct protein-protein interactions ( 9 , 10 ). (pnas.org)
  • Likewise, Apaf-1, a human protein that resembles C. elegans CED-4, interacts with caspase-9, a step that is required for the activation of the downstream protease caspase-3 ( 11 ). (pnas.org)
  • Mammalian IAP-1, -2, and XIAP directly bind and inhibit enzymatically active death proteases, caspase-3, and -7, but not the upstream protease caspase-8 ( 18 , 19 ). (pnas.org)
  • The CASP3 protein is a member of the cysteine-aspartic acid protease (caspase) family. (wikipedia.org)
  • It is an initiator caspase, critical to the apoptotic pathway found in many tissues. (wikipedia.org)
  • Activation of the Ras-Raf-MEK-ERK mitogen-activated protein kinase (MAPK) pathway is associated with protection of cells from apoptosis and inhibition of caspase-3 activation, although the targets are unknown. (nih.gov)
  • Here, we show that the ERK MAPK pathway inhibits caspase-9 activity by direct phosphorylation. (nih.gov)
  • This is through the release of Cytochrome c from mitochondria is a central event in the death receptor-independent, "intrinsic," apoptotic pathway which facilitates activation by Caspase 9 of the effector Caspases [1], which subsequently activates Caspase 3, and ultimately leads to the apoptotic cell death. (thefreedictionary.com)
  • Apoptosis triggered through the intrinsic pathway by radiation and anti-neoplastic drugs is initiated by the activation of caspase-9. (biochemj.org)
  • EG also activated the death receptor-dependent pathway of apoptosis by enhancing the expression of caspases-8, -9, and -3 and the Bcl-2 interacting domain (Bid). (mdpi.com)
  • Taken together, these results point to a general mechanism of apoptosis induction by resveratrol in ALL cells that involves a mitochondria/caspase-9-specific pathway for the activation of the caspase cascade and is independent of CD95-signaling. (aacrjournals.org)
  • ROS triggered the progression of apoptosis through activation of both the caspase-9-independent mitochondrial pathway and death receptor pathways, and the autophagy had an anti-apoptotic function in oridonin-treated HEp-2 cells. (spandidos-publications.com)
  • In regard to caspase 9 RNA splicing, a pathway linking the generation of de novo ceramide and the activation of PP1 to the regulation of the exclusion or inclusion of an exon 3,4,5,6 cassette of caspase 9 pre-mRNA was identified by our laboratory ( 14 ). (aacrjournals.org)
  • This effect required the generation of endogenous ceramide through the de novo pathway, and more importantly, inhibitors of protein phosphatase-1 abolished the ability of ceramide to affect the alternative splicing of caspase 9 ( 14 ). (aacrjournals.org)
  • In this dissertation, I discovered that the vaccinia virus (VACV)-encoded Bcl-2 homologue, F1L, directly inhibits caspase-9, the apical caspase in the mitochondrial cell death pathway, and NLRP1 (also known as NALP1), one of the inflammasome proteins that facilitates caspase-1 activation and cytokine secretion. (escholarship.org)
  • Caspase 9 is initiator CASP of internal apoptosis pathway and have important role in cancer development. (ac.ir)
  • Caspase-9 is an initiator caspase and plays an important role in the mitochondrial death pathway. (apexbt.com)
  • Caspase-9 (CASP-9) is an initiator CASP in the apoptosome-driven apoptosis pathway and plays an important role in the development and progression of cancer. (elsevier.com)
  • Loss of the initiator caspase of the intrinsic apoptotic pathway, caspase-9, however, did not promote cellular transformation. (mdpi.com)
  • Caspase-9 is the apex caspase of the mitochondrial pathway of apoptosis, which plays a critical role in apoptotic initiation and progression. (elsevier.com)
  • Caspase-8, -9, and -3 activity with downregulation of Bcl-2 illustrated occurrence of both intrinsic and extrinsic pathways in MCF7, while caspase-3 and -8 activity revealed extrinsic pathway of apoptosis, although Bcl-2 downregulated. (frontiersin.org)
  • In HeLa cells, the activity of caspase-9 and -3 and downregulation of Bcl-2 shows intrinsic pathway or mitochondrial pathway, whereas HepG2 shows caspase independent apoptosis. (frontiersin.org)
  • In Pcys-treated gut cell lines, caspase 8 (apoptosis extrinsic pathway) but not caspase 9 (apoptosis intrinsic pathway) is activated after 3 hours through P38 phosphorylation (90 min), emphasizing the potency of lowbush blueberry Pcys to eradicate gut TRAIL-resistant cancer cells. (hindawi.com)
  • Together with our finding that α-toxin induces cytochrome c release in intact cells and, interestingly, also from isolated mitochondria in a Bcl-2-controlled manner, our results demonstrate that S. aureus α-toxin triggers caspase activation via the intrinsic death pathway independently of death receptors. (rupress.org)
  • The main rout in apoptosis involves caspase signalling pathway. (medbiotech.net)
  • This extrinsic activation then triggers the hallmark caspase cascade characteristic of the apoptotic pathway, in which caspase-3 plays a dominant role. (wikipedia.org)
  • The specimens were labelled immunohistochemically for binding of an anti-caspase 9 primary antibody. (biomedsearch.com)
  • This peptide corresponds to 16 amino acids near the center of human Caspase-9.PEP-0029 can be used as a blocking peptide with polyclonal antibody PA5-19903. (fishersci.com)
  • Immunohistochemistry-Paraffin: Caspase-9 Antibody [NB100-56118] - Analysis Human Brain sections stained for cleaved Caspase-9 expression using this antibody at 1:2000. (novusbio.com)
  • Immunohistochemistry-Paraffin: Caspase-9 Antibody [NB100-56118] - Analysis of Capase-9 in mouse transplanted lung tumor section using anti-Caspase-9 antibody. (novusbio.com)
  • This antibody detects both the pro- and active-Caspase 9 forms. (novusbio.com)
  • The following antibody was used in this experiment: Phospho-Caspase 9 (Thr125) Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-36710, RRID AB_2553673. (thermofisher.com)
  • The Caspase 9 antibody was used by Krajewski's group to characterize caspase 9 mitochondrial release during cytochrome c-dependent apoptosis and ischemia in their neuronal cell culture models 1 . (novusbio.com)
  • Immunoblot studies with the Caspase 9 antibody allowed NIH researchers to dissect the complex signaling machinery downstream of cytochrome C, specifically that involving caspase 9 and Bax 2 . (novusbio.com)
  • Cowan et al employed the Caspase 9 antibody to classify in vivo activation of caspases 9 and 3 in olfactory receptor neurons (ORNs) and found that caspase 3 is required for normal bulb development as well as mature differentiation through targeted apoptosis 3 . (novusbio.com)
  • Further neurological studies with Caspase 9 antibody in the autosomal dominant progressive disorder Huntington's disease (HD) helped define caspases 2, 6, and 7 downstream pathways as those responsible for selective neuronal death 4 . (novusbio.com)
  • Herold's group used their characterization studies with Caspase 9 antibody to validate their preserved rat inguinal fat flap system as a permanent extracorporeal perfusion bioreactor system for examining fat cell death 5 . (novusbio.com)
  • Immunohistochemistry analysis of paraffin-embedded human lung carcinoma tissue, using Caspase 9 (Cleaved-Asp353) Antibody. (genetex.com)
  • Western blot analysis of extracts from NIH-3T3 cells, treated with Etoposide 25uM 60', using Caspase 9 (Cleaved-Asp353) Antibody. (genetex.com)
  • WB analysis of HeLa cells treated with Etoposide 25uM (60mins) lysate using GTX86928 Caspase 9 (cleaved Asp330) antibody. (genetex.com)
  • IHC-P analysis of human lung carcinoma tissue using GTX86928 Caspase 9 (cleaved Asp330) antibody. (genetex.com)
  • There are currently no references for Caspase 9 (cleaved Asp330) antibody (GTX86928) . (genetex.com)
  • Untreated and Staurosporine treated Jurkat cells were subjected to SDS PAGE followed by western blot with 10380-1-AP (Caspase 9/p35/p10 antibody) at dilution of 1:300 incubated at room temperature for 1.5 hours. (ptglab.com)
  • Immunohistochemical analysis of paraffin-embedded human heart tissue slide using 10380-1-AP (Caspase 9/p35/p10 antibody) at dilution of 1:50 (under 10x lens). (ptglab.com)
  • Immunohistochemical analysis of paraffin-embedded human heart tissue slide using 10380-1-AP (Caspase 9/p35/p10 antibody) at dilution of 1:50 (under 40x lens). (ptglab.com)
  • Immunofluorescent analysis of () fixed HepG2 cells using 10380-1-AP (Caspase 9/p35/p10 antibody) at dilution of 1:25 and Rhodamine-Goat anti-Rabbit IgG. (ptglab.com)
  • 1X10^6 HepG2 cells were stained with 0.2ug Caspase 9/p35/p10 antibody (10380-1-AP, red) and control antibody (blue). (ptglab.com)
  • The antibody will therefore detect pro-caspase-9 (as the motif is present) and the p10 caspase-9 fragment. (bio-rad-antibodies.com)
  • The anti-active caspase-9 antibody recognizes only the cleaved caspase-9 (37 kDa). (antibody-antibodies.com)
  • The affinity purified antibody recognizing the active forms of caspase-9 provides a new tool for identifying apoptotic cell populations in both tissue sections and cultured cells. (antibody-antibodies.com)
  • The microtiter plate has been pre-coated with a monoclonal antibody specific for caspase-9. (biobool.com)
  • Standards or samples are then added to the microtiter plate wells and caspase-9 if present, will bind to the antibody pre-coated wells, hi order to quantitatively determine the amount of caspase-9 present in the sample, a standardized preparation of horseradish peroxidase (HRP) -conjugated polyclonal antibody, specific for caspase-9 are added to each well to "sandwich" the caspase-9 immobilized on the plate. (biobool.com)
  • Only those wells that contain caspase-9 and enzyme-conjugated antibody will exhibit a change in color. (biobool.com)
  • Phospho-Caspase 9-S196 Antibody Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab) Applications WB, IHC, E antibody storage Gentaur recommends for long therm storage to freeze at -24 C. For short time storage up to 30 days we suggest fridge storage at 1 to 10 C. Prevent multiple freeze taw cycles of Phospho-Caspase 9-S196 Antibody Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab) Applications WB, IHC, E. (antibody-antibodies.com)
  • Phospho-Caspase 9-S196 Antibody Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab) Applications WB, IHC, E rabbit polyclonal These antibodies are very stable and can be stored up to 2 months at fridge temperature under 10C. (antibody-antibodies.com)
  • Do not freeze taw, rather use Phospho-Caspase 9-S196 Antibody Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab) Applications WB, IHC, E from the fridge if your use is less than 1 or 2 weeks. (antibody-antibodies.com)
  • Phospho-Caspase 9-S196 Antibody Peptide Affinity Purified Rabbit Polyclonal Antibody (Pab) Applications WB, IHC, E polyclonal antibodies polyclonal antobodies can be directed against a recombinant proteine, the natural protein or an epitope. (antibody-antibodies.com)
  • Western blot analysis of extracts of HeLa cells using Caspase-9 Polyclonal Antibody at dilution of 1:1000. (elabscience.com)
  • Immunohistochemistry of paraffin-embedded Human colon carcinoma using Caspase-9 Polyclonal Antibody at dilution of 1:100 (40x lens). (elabscience.com)
  • Standards and test samples are added to the wells and along with a Caspase-9 detection antibody and the microplate is then incubated at room temperature. (abcam.cn)
  • Caspase-9 is essentially localized in mitochondria, the disruption of the outer mitochondrial membrane occurring early during apoptosis is critical for its subcellular redistribution and activation. (biovendor.com)
  • Nevertheless, the timing and caspase-dependence of mitochondrial membrane depolarization differed considerably after CD95- or BCR-triggering. (nih.gov)
  • In this report, we demonstrate that in HL-60/Apaf-1 cells, the activity of caspase-9 and -3 induced by Apaf-1 overexpression was associated with a significant increase (5-fold) in the cytosolic accumulation of cytochrome c (cyt c ), loss of mitochondrial membrane potential (ΔΨm), and an increase in the reactive oxygen species. (aacrjournals.org)
  • This mechanism may involve a cytosolic mitochondrial permeability transition factor, which may be processed and activated by the downstream effector caspases, thereby completing an amplifying feedback loop, which triggers the mitochondrial events during apoptosis. (aacrjournals.org)
  • Two main evolutionarily conserved protein families are involved in apoptosis, namely members of the Bcl-2 protein family, which control mitochondrial integrity ( Youle and Strasser, 2008 ), and caspases, which mediate the execution phase of apoptosis ( Fuentes-Prior and Salvesen, 2004 ). (biologists.org)
  • The findings revealed that the TαPcZn-PDT treatment of LoVo cells resulted in the induction of apoptosis, the formation of p38 MAPK/caspase-9 complexes, the activation of p38 MAPK, caspase-9, caspase-3 and Bid, the downregulation of Bcl-2, the reduction of mitochondrial membrane potential (ΔΨm), the upregulation of Bax and the release of apoptosis-inducing factor (AIF) and cytochrome c (Cyto c). (spandidos-publications.com)
  • MitoCasp A simultaneous dual parameter Assay For: Mitochondrial Membrane Potential Detection & Caspase (poly, 3/7, 8, 9, 1) Activity. (celltechnology.com)
  • Simultaneous detection of mitochondrial membrane potential and caspase activity. (celltechnology.com)
  • Utilizing these two reagents in combination Caspase activity and mitochondrial membrane potential can be analyzed simultaneously. (celltechnology.com)
  • Our results from Western blotting suggest that emodin triggered apoptosis of WEHI-3 cells through the endoplasmic reticulum (ER) stress, caspase cascade-dependent and -independent mitochondrial pathways. (nih.gov)
  • Mitochondrial disruption during apoptosis results in the release of cytochrome c that forms apoptosomes with Apaf-1 and caspase-9. (houstonmethodist.org)
  • Caspase-3 is activated in the apoptotic cell both by extrinsic (death ligand) and intrinsic (mitochondrial) pathways. (wikipedia.org)
  • Apoptotic signals cause the release of cytochrome c from mitochondria and activation of apaf-1 (apoptosome), which then cleaves the pro-enzyme of caspase-9 into the active dimer form. (wikipedia.org)
  • Within the cell, caspase-9 in humans is found in the mitochondria, cytosol, and nucleus. (wikipedia.org)
  • Caspase 9 is active as a heterotetramer, is present in the cytosol and, upon activation, translocates to the mitochondria. (fishersci.com)
  • Both pro and active/cleaved Caspase-9 staining may also be seen in the mitochondria. (novusbio.com)
  • Induction of stress signalling pathways JNK/SAPK causes release of cytochrome c from mitochondria and activation of apaf-1 (apoptosome), which in turn cleaves the pro-enzyme of caspase-9 into the active form. (creativebiomart.net)
  • However, the manner in which p38 MAPK and caspase-9 are involved in the regulation of mitochondria-mediated apoptosis in the TαPcZn-PDT-treated LoVo human colon carcinoma cells remains unclear. (spandidos-publications.com)
  • These findings indicated that p38 MAPK plays the major regulatory role in the crosstalk between p38 MAPK and caspase-9 and that direct interaction between p38 MAPK and caspase-9 may regulate mitochondria-mediated apoptosis in the TαPcZn-PDT-treated LoVo cells. (spandidos-publications.com)
  • Unlike Bcl-2, MIHA functioned after release of cytochrome c and DIABLO from the mitochondria and was able to bind to both processed caspase 9 and processed caspase 3 to prevent feedback activation of their zymogen forms. (rupress.org)
  • Upon induction of apoptosis, Cytochrome c released from mitochondria associates with pro-caspase-9 (47 kDa) and Apaf-1. (antibody-antibodies.com)
  • Downstream of caspase 8, the apoptotic signaling cascade bifurcates into a mitochondria-independent caspase 8/caspase 3 arm and a mitochondria-dependent, caspase 8/Bid/Bax/Bak/cytochrome c arm. (elsevier.com)
  • In intrinsic activation, cytochrome c from the mitochondria works in combination with caspase-9, apoptosis-activating factor 1 (Apaf-1), and ATP to process procaspase-3. (wikipedia.org)
  • Caspase-9 belongs to a family of caspases, cysteine-aspartic proteases involved in apoptosis and cytokine signalling. (wikipedia.org)
  • 1997). Substrate specificities of caspase family proteases. (anaspec.com)
  • Here we show that a mammalian homolog of CED-4, Apaf-1, can associate with several death proteases, including caspase-4, caspase-8, caspase-9, and nematode CED-3 in mammalian cells. (pnas.org)
  • A family of cysteine proteases (designated caspases) related to the C. elegans CED-3 appears to represent the effector arm of the apoptotic program ( 13 ). (pnas.org)
  • The region of homology shared between Apaf-1 and the prodomains of CED-3-like proteases has been termed caspase recruitment domain ( 19 ). (pnas.org)
  • Caspases are cysteine proteases, expressed as inactive precursors, that mediate apoptosis by proteolysis of specific substrates. (fishersci.com)
  • Cell death signals are transduced by death domain containing adapter molecules and members of the caspase family of proteases. (novusbio.com)
  • Caspases constitute a family of cysteine proteases centrally involved in programmed cell death, which is an integral part of normal embryonic and fetal development. (sigmaaldrich.com)
  • Caspases are intracellular proteases that function as initiators and effectors of apoptosis. (sciencemag.org)
  • As is common with other proteases, caspases are synthesized as precursors that undergo proteolytic maturation, either autocatalytically or in a cascade by enzymes with similar specificity (5). (celltechnology.com)
  • The mammalian cell death proteases have been divided into proximal and distal caspases based on the their sites of action in the proteolytic caspase cascade ( 6 ). (pnas.org)
  • Apoptosis is ultimately carried out by the sequential activation of initiator and executioner caspases, which constitute a family of intracellular proteases involved in dismantling the cell in an ordered fashion. (mdpi.com)
  • Caspases are the proteases responsible for dismantling the cell in an ordered and histologically distinct process termed apoptosis [ 1 ]. (mdpi.com)
  • Different protein isoforms of caspase-9 are produced due to alternative splicing. (wikipedia.org)
  • In mammalian cell extracts, cytochrome c-induced activation of caspases-9 and -3 requires okadaic-acid-sensitive protein phosphatase activity. (nih.gov)
  • CED-4 interacts with CED-3 and CED-9 forming a multimeric protein complex ( 7 - 9 ). (pnas.org)
  • Human Caspase 9 recombinant protein catalytic subunits (NP_001220). (novusbio.com)
  • Additionally we are shipping Caspase 9 Kits (75) and Caspase 9 Proteins (20) and many more products for this protein. (antibodies-online.com)
  • We report here the purification of the third protein factor, Apaf-3, that participates in caspase-3 activation in vitro. (nih.gov)
  • Thus, caspases can be directly regulated by protein phosphorylation. (sciencemag.org)
  • Protein level changes of procaspase 8, procaspase 9 and cleaved caspase 9 were determined by Western blot. (arvojournals.org)
  • We demonstrate that, in the absence of Shh, Ptc recruits a protein complex that includes DRAL, one of the caspase recruitment (CARD)-domain containing proteins TUCAN (family member, 8) or NALP1 (NLR family, pyrin domain containing 1) and apical caspase-9. (inserm.fr)
  • Apoptosis was assessed using Annexin- V/PI assays, whereas protein levels of p53, caspase 3, caspase 9, caspase 8 and Bcl2 were evaluated by western blotting. (eurekaselect.com)
  • Specifically, ceramide treatment resulted in an increase in the pro-apoptotic caspase 9a MRNA mRNA and protein levels with concomitant decrease in caspase 9b (cassette exclusion) mRNA and protein levels in A549 cells ( 14 ). (aacrjournals.org)
  • The involvement of PP1 and endogenous ceramide in the dephosphorylation of SR proteins and the effects on caspase 9 alternative splicing suggested that at least 1 SR protein isoform regulated the alternative splicing mechanism of caspase 9. (aacrjournals.org)
  • Indeed, in further mechanistic studies, our laboratory identified 1 SR protein, SRSF1 (also known as SRp30a), as a critical splicing factor in the alternative splicing of caspase 9 pre-mRNA in A549 lung adenocarcinoma cells ( 15 ). (aacrjournals.org)
  • Results show that mRNA and protein levels of HAX-1 in prostate cancer cell lines were significantly higher and inhibits cell apoptosis through caspase-9 inactivation. (nih.gov)
  • However, it remains largely unknown how apparently disparate events implicated in apoptosis, such as oxidative stress, ionic dysregulation, and activation of mitogen-activated protein kinases (MAPK) and caspases, signal among one another to initiate and propagate cell death. (jneurosci.org)
  • The dsRNA-induced apoptosis is potentiated by the inhibition of protein synthesis, whose role is to accelerate the execution of all apoptosis steps downstream of, and including, the activation of caspase 8. (elsevier.com)
  • Thus, efficient apoptosis in response to viral dsRNA results from the co-operation of the two major apical caspases (8 and 9) and the dsRNA-activated protein kinase R (PKR)/ribonuclease L (RNase L) system that is essential for the inhibition of protein synthesis in response to viral infection. (elsevier.com)
  • After 24 hours, we detected the protein levels of cleaved Caspase-3 by Western Blot. (apexbt.com)
  • The prodomains of several apical caspases contain a protein module termed caspase recruitment domain (CARD) that is conserved in several apoptosis regulatory molecules, including Apaf-1, RAIDD, and cellular inhibitors of apoptosis proteins (IAPs) ( 12 ). (pnas.org)
  • The rat caspase-9 cDNA of 2058 bp predicts a protein of 454 amino acids, which contains a caspase-recruitment domain ('CARD') at the N-terminus and enzymic domains at the C-terminus. (elsevier.com)
  • Furthermore, α-toxin-induced caspase activation in CD95-resistant Jurkat sublines lacking CD95, Fas-activated death domain, or caspase-8 but not in cells stably expressing the antiapoptotic protein Bcl-2. (rupress.org)
  • Caspases orchestrate the organized death of the cell by cleaving a small but specific complement of protein substrates. (jneurosci.org)
  • Caspase-3 is a caspase protein that interacts with caspase-8 and caspase-9. (wikipedia.org)
  • and the protein itself is processed and activated by caspases 8, 9, and 10. (wikipedia.org)
  • Caspase-activated DNase (CAD) or DNA fragmentation factor subunit beta is a protein that in humans is encoded by the DFFB gene. (wikipedia.org)
  • Caspase 3 is responsible for cellular differentiation, although it is unclear how this kind of protein can promote the cell apoptosis. (wikipedia.org)
  • Similar to other caspases, caspase-9 has three domains: N-terminal pro-domain, large subunit, and a small subunit. (wikipedia.org)
  • The caspase-9 monomer consists of one large and one small subunit, both comprising the catalytic domain. (wikipedia.org)
  • Akt can act on both processed and unprocessed caspase-9 in-vitro, where phosphorylation on processed caspase-9 occurs on the large subunit. (wikipedia.org)
  • In western blots, the proform of caspase-9 is detected at ~50 kDa, the large subunit at ~35 kDa, and the small subunit at ~15 kDa. (novusbio.com)
  • Caspases are synthesized as inactive proenzymes comprising an N-terminal peptide together with one large and one small subunit. (biovendor.com)
  • The apoptotic status of the mouse tumor tissue was verified by immunohistochemical techniques staining for cleaved caspase-3 p11 subunit. (ku.edu)
  • The complex processes pro-caspase-9 into a large subunit (37 kDa/17 kDa) and a small subunit (10 kDa). (antibody-antibodies.com)
  • The large and small subunit associate with each other to form an active heterodimer caspase. (wikipedia.org)
  • Bcl-2 and Bcl-X L , two members of the Bcl-2 family, function as apoptosis inhibitors and are considered homologs of the nematode CED-9 ( 15 ). (pnas.org)
  • Several studies have shown that these apoptosis inhibitors regulate the activation of caspases ( 16 , 17 ). (pnas.org)
  • However, the viral proteins CrmA and p35, although potent inhibitors of recombinant caspase-9, had almost no ability to block caspase-9 in this system. (biochemj.org)
  • We hypothesize that the viral inhibitors CrmA and p35 are excluded from reacting productively with the natural form of active caspase-9 in vivo , making the potency of inhibitors highly context-dependent. (biochemj.org)
  • Intrigued by the multiple ways to control caspase-9's activity, we sought after designing synthetic caspase-9 inhibitors in addition to defining the mechanistic details metal regulation and CARD domain activation. (umass.edu)
  • Through exploring these underlying molecular details behind the various mechanisms, not only has the field of caspase-9 regulation mechanisms been extended, essential information was gained for further pursuit in an advancement towards the design of caspase-9 activators and inhibitors. (umass.edu)
  • Caspase inhibitors play an important role in investigating biological processes. (scbt.com)
  • The methodology is based on carboxyfluorescein (FAM) labeled fluoromethyl ketone (FMK)-peptide inhibitors of caspases. (celltechnology.com)
  • In contrast, simultaneous exposure of Lovo and WiDr cells to AG337 and inhibitors of caspases 8, 9 and 3 caused a decrease in the number of apoptotic cells compared with AG337 exposure alone. (elsevier.com)
  • Compounds to be screened can directly be added to the reaction and the level of inhibition of caspase 9 activity can be determined by comparison of the fluorescence intensity in samples with and without the testing inhibitors. (abcam.cn)
  • Second, in tumor cells caspases might be kept in check by cellular caspase inhibitors such as c-FLIP or XIAP. (mdpi.com)
  • We used these methods to identify potent substrate inhibitors of caspase-9. (medbiotech.net)
  • Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK. (nih.gov)
  • We suggest that phosphorylation and inhibition of caspase-9 by ERK promotes cell survival during development and tissue homeostasis. (nih.gov)
  • Reduced caspase activity was not due to lower concentrations of pro-Casp3 but correlated with inhibition of proteolytic processing of pro-Casp3 ( Fig. 1 B) ( 4 ), implying a defect at or upstream of this caspase. (sciencemag.org)
  • Altogether, our data strongly indicate that the inhibition of ceramide conversion to complex sphingolipids by D609 is accompanied by an enhancement of FasL-induced caspase-dependent and -independent cell death in T lymphocytes. (mdpi.com)
  • Based on known mechanisms, such as the unique inhibitory complex of caspase-9 and XIAP-BIR3, development of synthetic regulators can be envisioned, while other mechanisms such as zinc-mediated inhibition and CARD activation of caspse-9 remain undefined. (umass.edu)
  • The activation of caspase-9 preceded that of caspase-8 and its specific inhibition completely prevented apoptosis. (oup.com)
  • We identified two conserved motifs at the N- terminus of F1L preceding the Bcl-2-like domain by mutagenesis studies that are responsible for interaction and inhibition of caspase-9 and NLRP1, respectively. (escholarship.org)
  • Inhibition of Caspase-9 restricted, while Apaf-1 promoted, Chlamydia pneumoniae infection in HEp-2, HeLa, and mouse epithelial fibroblast (MEF) cells. (nih.gov)
  • interaction of rmEMMPRINex with U937 cells leads to inhibition of MCT1 membrane expression, intracellular activation of procaspase-9, followed by DNA fragmentation and apoptosis. (nih.gov)
  • Inhibition of Mcl-1 and activation of caspases are critically involved in gallotannin-induced apoptosis in prostate cancer cells. (nih.gov)
  • We aimed to clarify whether activation of caspases and Fas signalling are crucial for the onset of apoptosis after specific inhibition of TS and whether p53 plays a role in activation of these downstream processes. (elsevier.com)
  • In conclusion, these results indicate that apoptosis induced after specific inhibition of TS is mediated via the caspases, but without clear involvement of Fas signalling. (elsevier.com)
  • Indeed, an early robust increase in TEA-sensitive potassium channel currents induced by DTDP is attenuated by p38 inhibition but not by caspase inhibition. (jneurosci.org)
  • Note that in addition to apoptosis, Caspase-8 is also required for the inhibition of another form of programmed cell death called Necroptosis . (wikipedia.org)
  • Inhibition of caspases can delay apoptosis, implicating a potential role in drug screening efforts. (abcam.cn)
  • Caspase-9 inhibition provided neurofunctional protection and established caspase-6 as its downstream target. (elsevier.com)
  • Collectively, these results support selective inhibition of these specific caspases as an effective therapeutic strategy for stroke. (elsevier.com)
  • Consistent with the inhibition of caspase-8, ARC attenuated apoptosis induced by FADD and TRADD and that triggered by stimulation of death receptors coupled to caspase-8, including CD95/Fas, tumor necrosis factor-R1, and TRAMP/DR3. (pnas.org)
  • As caspase-9 function as an initiator in the caspase-cascade, so inhibition of this caspase can stop apoptosis or slow down it. (medbiotech.net)
  • Therefore it remains important to gain a detailed understanding of the mechanisms behind native caspase-9 regulatory pathways and harness these mechanisms for therapeutic purposes. (umass.edu)
  • Historically, the regulation of the alternative splicing of caspase 9 by signaling pathways began with the lipid second messenger, ceramide. (aacrjournals.org)
  • These data suggest that emodin triggered apoptosis of WEHI-3 cells through the ROS and caspase-dependent pathways. (nih.gov)
  • Third, pathways upstream of caspase activation might be disrupted in tumor cells. (mdpi.com)
  • Based on their structure and order in cell death pathways, caspases can be divided into initiator and effector caspases. (rupress.org)
  • The caspase family of proteins function as key components of the apoptotic machinery and act to destroy specific target proteins which are critical to cellular longevity. (scbt.com)
  • Thus, both the phospho-state of SR proteins and the alternative splicing of caspase 9 are regulated by the generation of de novo ceramide and subsequent PP1 activation ( 14 ). (aacrjournals.org)
  • Tumour growth can occur by a combination of factors, including a mutation in a cell cycle gene which removes the restraints on cell growth, combined with mutations in apoptopic proteins such as Caspases that would respond by inducing cell death in abnormally growing cells. (wikipedia.org)
  • The CARD has been proposed to play a regulatory role in apoptosis by allowing proteins such as Apaf-1 to associate with caspase-9 ( 13 ). (pnas.org)
  • Two viral proteins, baculovirus p35 and cowpox virus CrmA, inhibit apoptosis by directly targeting caspases ( 14 , 15 ). (pnas.org)
  • By cleaving critical proteins, caspases lead to the changes that characterize apoptosis both morphologically and biochemically, such as chromatin condensation, loss of cell adhesion, cell shrinkage, membrane blebbing, DNA fragmentation, and finally formation of apoptotic bodies, which stimulate their own engulfment by phagocytes. (mdpi.com)
  • These molecules are sufficient to activate caspase-3 in vitro, but other regulatory proteins are necessary in vivo. (wikipedia.org)
  • These studies uncovered a nonapoptotic role for the initiator caspase-9 in primitive blood formation. (sigmaaldrich.com)
  • These data reveal a novel nonapoptotic function for the initiator caspase-9 and, for the first time, implicate nonapoptotic caspase activity in primitive blood formation. (sigmaaldrich.com)
  • As an executioner caspase, the caspase-3 zymogen has virtually no activity until it is cleaved by an initiator caspase after apoptotic signaling events have occurred. (wikipedia.org)
  • Ready-to-use colorimetric substrate for caspase-9/Mch6 and related caspases that recognize the amino acid sequence LEHD. (antibody-antibodies.com)
  • Activated caspase-9 in turn cleaves and activates caspase-3. (nih.gov)
  • Activated caspase 9 primary signaling occurs through caspase 3, which it cleaves and activates. (novusbio.com)
  • In apoptosis, caspases are responsible for proteolytic cleavages that lead to cell disassembly (effector caspases), and are involved in upstream regulatory events (initiator caspases). (celltechnology.com)
  • Activated initiator caspases then process effector caspases, such as Caspase 3 and Caspase 7, which in turn cause cell collapse. (abcam.cn)
  • Once activated, caspase-9 goes on to cleave caspase-3, -6, and -7, initiating the caspase cascade as they cleave several other cellular targets. (wikipedia.org)
  • Caspase 9 is responsible for initiating the caspase activation cascade during apoptosis. (biomedsearch.com)
  • Several caspases including caspase-4, -8, and -9 structurally resemble CED-3 in that they contain long prodomains and appear to act upstream in the caspase cascade ( 13 , 14 ). (pnas.org)
  • Caspase 9 is involved in the caspase activation cascade responsible for apoptosis execution and cleaves/activates Caspase 3 and Caspase 6. (fishersci.com)
  • Further, Caspase 9 is involved in the activation cascade of caspases responsible for apoptosis execution. (fishersci.com)
  • this step is thought to be one of the earliest in the caspase activation cascade. (genetex.com)
  • Cytochrome c/Apaf-1/caspase-9 form a socalled apoptosome, amplifying the caspase cascade. (biovendor.com)
  • The central component of this process is a cascade of proteolytic enzymes called caspases. (celltechnology.com)
  • In HL-60 cells apoptosis was mediated by the activation of the caspase-3 cascade. (oup.com)
  • Cleaved caspase-9 further processes other caspases including caspase-3 and caspase-6, to initiate a caspase cascade leading to apoptosis. (antibody-antibodies.com)
  • Involved in the activation cascade of caspases responsible for apoptosis execution. (abcam.cn)
  • Activation of caspase-9 by dimerization in apoptosomes then triggers a caspase signaling cascade. (houstonmethodist.org)
  • These results have a similar profile for Caspase 9 , in which tiliroside activates Caspase 9 and doxorubicin did not activate it. (thefreedictionary.com)
  • Thus, patients who develop GvHD after infusion of allodepleted donor-derived T cells expressing an inducible human caspase 9 (iC9) had their disease effectively controlled by a single administration of a small-molecule drug (AP1903) that dimerizes and activates the iC9 transgene. (bloodjournal.org)
  • These events were secondary to the activity of the downstream caspases induced by Apaf-1. (aacrjournals.org)
  • Upon formation of the death-inducing signaling complex or the apoptosome, pro-caspase-8 or -9, respectively, are autoproteolytically processed, resulting in the activation of downstream caspases. (rupress.org)
  • 8 and Caspase 9 colorimetric assay: R&D Systems, Inc. (thefreedictionary.com)
  • The influence of compound 3 on caspase 3/7, caspase 8 and caspase 9 activity in CCRF-CEM leukemia cells was detected using Caspase-Glo 3/7, Caspase-Glo 8 and Caspase-Glo 9 Assay kits (Promega, Germany). (thefreedictionary.com)
  • The influence of compounds 2-4 on caspase 3/7, caspase 8 and caspase 9 activity in CCRF-CEM leukemia cells was detected using Caspase-Glo 3/7, Caspase-Glo 8 and Caspase-Glo 9 Assay kits (Promega, Germany). (thefreedictionary.com)
  • Caspase-Glo 9 Assay System - Apoptosis Assays and Systems, Promega - Model FPPAG8210 - Each : Apo-ONE Homogeneous Caspase-3/7 Assay: Use for fast, sensitive, fluorescent measurement of caspase-3 and -7 activity in a homogenous format. (egeneralmedical.com)
  • Product Description specifical Principle of the Assay: caspase-9 ELISA kit applies the quantitative sandwich enzyme irnmunoassay technique. (biobool.com)
  • Abcam's Caspase-9 Human in vitro ELISA (Enzyme-Linked Immunosorbent Assay) kit is designed for accurate quantitative measurement of Human Caspase-9 concentrations in cell lysate, cell culture supernatant and serum. (abcam.cn)
  • Apoptosis as the mechanism of cell death was confirmed by morphology study, caspases activity assay, as well as apoptosis related gene expression, Bcl-2 . (frontiersin.org)
  • 2. Caspase antibodies are classical tools for detecting inactive (pro) and active (cleaved) forms of the enzymes. (novusbio.com)
  • Caspase-9 specific antibodies have been precoated onto 96-well plates. (abcam.cn)
  • We also demonstrate that S. aureus -induced cell death and caspase activation were mediated by α-toxin, a major cytotoxin of S. aureus , since both events were abrogated by two different anti-α-toxin antibodies and could not be induced with supernatants of an α-toxin-deficient S. aureus strain. (rupress.org)
  • Cyto c induces caspase activation when added to cytosolic extracts in vitro with deoxyadenosine triphosphate (dATP) ( 1 ). (sciencemag.org)
  • Kim W-H, Song H-O, Choi H-J, Bang H-I, Choi D-Y, Park H. Ethyl Gallate Induces Apoptosis of HL-60 Cells by Promoting the Expression of Caspases-8, -9, -3, Apoptosis-Inducing Factor and Endonuclease G. International Journal of Molecular Sciences . (mdpi.com)
  • Recombinant Multivalent EMMPRIN Extracellular Domain Induces U937 Human Leukemia Cell Apoptosis by Downregulation of Monocarboxylate Transporter 1 and Activation of Procaspase-9. (nih.gov)
  • The temporal and spatial pattern of expression demonstrates that neuronal caspase-9 activity induces caspase-6 activation, mediating axonal loss by 12 hpr followed by neuronal death within 24 hpr. (elsevier.com)
  • Gamma tocopheryl quinone induces apoptosis in cancer cells via caspase-9 activation and cytochrome c release. (unicatt.it)
  • The ced-9 gene functions upstream of ced-3 and ced-4 and protects cells that normally survive programmed cell death during worm development ( 5 , 6 ). (pnas.org)
  • In particular, we observed a time- and dose-dependent increase in the activities of the upstream caspase-9 and caspase-8 and of the downstream caspase-3. (oup.com)
  • however, GSE caused both caspase-dependent and caspase-independent apoptosis as evidenced by cytochrome c and apoptosis-inducing factor release into cytosol. (aacrjournals.org)
  • In addition, other apoptosis signaling molecules released from the mitochondrion, such as apoptosis-inducing factor and endonuclease G, may induce caspase-9-independent apoptosis. (houstonmethodist.org)
  • Furthermore, Apaf-1 promoted the processing and activation of caspase-9 in vivo . (pnas.org)
  • Activation of caspase 9 and 8 occurred even at low concentration of PA, but caspase 3/7 activation occurred only at high concentration treatment. (thefreedictionary.com)
  • Sevoflurane postconditioning prevents activation of caspase 3 and 9 through antiapoptotic signaling after myocardial ischemia-reperfusion. (sigmaaldrich.com)
  • drugs blocking the activation of Caspase-1 have been used to improve the health of patients. (wikipedia.org)
  • The result showed that Z-LEHD-FMK could significantly inhibit the activation of Caspase-3 induced by Drug A, which indicated that activation of Caspase-3 induced by Drug A is Caspase-9 dependent. (apexbt.com)
  • Activation of caspase-9 and its influencing factors in beef during conditioning. (ac.ir)
  • To determine the signaling events induced by caspase-9, we used chemically induced dimerization for specific activation of caspase-9. (houstonmethodist.org)
  • Mangosteen (Garcinia mangostana) extract has been shown to inhibit the activation of caspase 3 in B-amyloid treated human neuronal cells. (wikipedia.org)
  • Moreover, resistance to cyto c-mediated activation of caspases was not an artifact of over-expressing oncogenic Ras, because extracts from DLD-1 colon cancer cells, which contain an endogenous activated Ki-Ras gene, displayed similar resistance to cyto c. (sciencemag.org)
  • Activated caspases cleave their recognition site, freeing the chimeric GAL4VP16 transcription factor, which can then translocate to the nucleus, where it initiates the transcription of the eGFP reporter gene. (biologists.org)
  • We designed a caspase-reporting system based on the transcriptional induction of the eGFP gene. (biologists.org)
  • The purpose of this study was to use laser capture microdissection (LCM) to isolate RGC coupled with real-time PCR to test the hypothesis that gene expression of initiator caspases would be elevated during RGC death in experimental glaucoma. (arvojournals.org)
  • Silver nanoparticles biosynthesized using Achillea biebersteinii flower extract: apoptosis induction in MCF-7 cells via caspase activation and regulation of Bax and Bcl-2 gene expression. (nih.gov)
  • Polymorphism of CASP 9 gene promoter could influence the gene activity and cause sensitivity to cancer. (ac.ir)
  • Materials and methods: In this case-control study, 100 patients with gastric cancer and 100 normal subjects were considered for caspase 9 promoter gene polymorphism. (ac.ir)
  • Polymorphisms in the promoter region of the CASP-9 gene may influence the promoter activity of this gene, thereby modulating susceptibility to lung cancer. (elsevier.com)
  • In cancer, therefore, one would anticipate caspases to be frequently rendered inactive, either by gene silencing or by somatic mutations. (mdpi.com)
  • However, gene regulation of caspase-9 is largely unknown. (elsevier.com)
  • Here we have cloned the full-length cDNA of rat caspase-9 and have isolated promoter regions of this gene. (elsevier.com)
  • When cloned into reporter gene vectors, the genomic segment showed significant promoter activity, indicating that the 5′-flanking regions isolated by genomic walking contain the gene promoter of rat caspase-9. (elsevier.com)
  • When TET1 gene in glioma U251 cells was knocked down by CRISPR/Caspase-9 system, the proliferation and invasive ability of U251 increased remarkably. (portlandpress.com)
  • This study is a phase I dose finding trial to determine if chimeric antigen receptor T (CAR-T) cells targeting the CD19 antigen and containing the inducible caspase 9 safety switch can be safely administered to adult subjects with relapsed or refractory B-cell Lymphoma. (clinicaltrials.gov)
  • Processing occurs when the apoptosome binds to pro-caspase-9 as apaf-1 assists in the autoproteolytic processing of the zymogen. (wikipedia.org)
  • Activation occurs when caspase-9 dimerizes, and there are two different ways for which this can occur: Caspase-9 is auto-activated when it binds to apaf-1(apoptosome), as apaf-1 oligomerizes the precursor molecules of pro-caspase-9. (wikipedia.org)
  • Caspase-9, formerly called Apaf-3, binds to Apaf-1 in the presence of cytochrome c and dATP, which leads to caspase-9 activation. (biovendor.com)
  • We provide multiple lines of evidence that F1L directly and selectively binds and suppresses caspase-9 and NLRP1. (escholarship.org)
  • When released, cytosolic cytochrome c binds together with dATP and the apoptosis-activating factor-1 to pro-caspase-9 to form the apoptosome. (rupress.org)
  • Previously activated caspases can cleave caspase-9, causing its dimerization. (wikipedia.org)
  • Homology between the sense portion of the siRNA sequence and the mRNA enables the nuclease enzyme to bind and cleave the caspase transcript into small pieces, which are degraded by the cell's machinery. (abcam.com)
  • Once initiated caspase-9 goes on to cleave procaspase-3 & procaspase-7 and which cleave several cellular targets, including poly ADP ribose polymerase. (creativebiomart.net)
  • Caspases have the ability to cleave after aspartic acid residues. (abcam.cn)
  • Once released into the cytosol, DIABLO bound to MIHA and disrupted its association with processed caspase 9, thereby allowing caspase 9 to activate caspase 3, resulting in apoptosis. (rupress.org)
  • Proapoptotic signals autocatalytically activate initiator caspases, such as Caspase 8 and Caspase 9. (abcam.cn)
  • One such signaling event is the introduction of granzyme B, which can activate initiator caspases, into cells targeted for apoptosis by killer T cells. (wikipedia.org)
  • Tissue expression of caspase-9 is ubiquitous with the highest expression in the brain and heart, specifically at the developmental stage of an adult in the heart's muscle cells. (wikipedia.org)
  • The caspase 9 positive cell fraction was calculated for both epidermal and dermal cells in psoriatic lesions and healthy control skin. (biomedsearch.com)
  • Caspase-9 is phosphorylated at Thr 125, a conserved MAPK consensus site targeted by ERK2 in vitro, in a MEK-dependent manner in cells stimulated with epidermal growth factor (EGF) or 12-O-tetradecanoylphorbol-13-acetate (TPA). (nih.gov)
  • Bcl-X L , an antiapoptotic member of the Bcl-2 family, was shown to physically interact with Apaf-1 and caspase-9 in mammalian cells. (pnas.org)
  • Expression of Bcl-X L inhibited the association of Apaf-1 with caspase-9 in mammalian cells. (pnas.org)
  • Significantly, recombinant Bcl-X L purified from Escherichia coli or insect cells inhibited Apaf-1-dependent processing of caspase-9. (pnas.org)
  • Cytosolic extracts from Ras(V12)-expressing cells are refractory to cyto c-induced caspase activation. (sciencemag.org)
  • D609 stimulated FasL-induced cell death in caspase-8-deficient Jurkat cells, indicating that D609 acts downstream of caspase-8. (mdpi.com)
  • By expression in 293 cells we addressed the potential of candidate initiator caspases to function in the presence of zVAD, and found that caspase-9 efficiently processed caspase-3, while caspase-2 or -8 were inactive. (nih.gov)
  • Therefore, oridonin has the potential to be developed as an anticancer agent, and the combination of oridonin with those agents leading to reduction of caspase-9 expression in tumor cells could represent a novel approach to human laryngeal cancer treatment. (spandidos-publications.com)
  • Jurkat cells were treated with 1 µM staurosporine to induce caspase 9 activity (top), or treated with a control (bottom). (neuromics.com)
  • Almost all cells in the induced sample (top) fluoresce green therefore they have activated caspase 9. (neuromics.com)
  • Sharula and Zhongjun Wu*, "Regulation of Apoptosis by SYB in HepG2 Liver Cancer Cells is Mediated by the P53/Caspase 9 Axis", Anti-Cancer Agents in Medicinal Chemistry (2017) 17: 941. (eurekaselect.com)
  • To further determine the biological importance of this mechanism, we employed RNA oligonucleotides to redirect caspase 9 pre-mRNA splicing in favor of caspase 9b expression, which resulted in an increase in the IC 50 of non-small cell lung cancer (NSCLC) cells to daunorubicin, cisplatinum, and paclitaxel. (aacrjournals.org)
  • Transforming growth factor beta-dependent sequential activation of Smad, Bim, and caspase-9 mediates physiological apoptosis in gastric epithelial cells. (semanticscholar.org)
  • Emodin stimulated the activities of caspase-3 and -9 of WEHI-3 cells. (nih.gov)
  • Cells were determined the caspase-3, -8, and -9 activity (a) and percentage of viable cells (b) as described in Section 2. (nih.gov)
  • Caspases are synthesized as inactive pro-enzymes that are processed to active form in cells undergoing apoptosis. (antibody-antibodies.com)
  • In cells, F1L specifically represses caspase-9- dependent apoptosis and NLRP1-dependent IL-1[Beta] secretion. (escholarship.org)
  • Expression of mutant caspase-9 correlated with a downregulation of BAFFR (B-cell-activating factor belonging to the TNF family (BAFF) receptor) in B cells and ICOS (inducible T-cell costimulator) in T cells. (nih.gov)
  • Levels of caspase-9, caspase-10, MAVS, and pIRF7 in mononuclear cells and the disease activity index (SLEDAI) in the systemic lupus erythematosus patients were determined. (nih.gov)
  • caspase-9 mediates Puma activation to determine the threshold for overcoming chemoresistance in cancer cells. (nih.gov)
  • Additionally, scientists have used caspases as cancer therapy to kill unwanted cells in tumours. (wikipedia.org)
  • Further analysis showed that the enzymatic activity of caspase-8 was inhibited by ARC in 293T cells. (pnas.org)
  • We discuss several possible ways how tumor cells might evade the need for alterations of caspase genes. (mdpi.com)
  • First, alternative splicing in tumor cells might generate caspase variants that counteract apoptosis. (mdpi.com)
  • We thus propose a model wherein caspases are preserved in tumor cells due to their functional contributions to development and progression of tumors. (mdpi.com)
  • We show that caspase activation and DNA fragmentation were induced not only when Jurkat T cells were infected with intact bacteria, but also after treatment with supernatants of various S. aureus strains. (rupress.org)
  • Low levels of caspase-7 expression and activation correlate with lack of DNA fragmentation in 129- Casp3 -/- apoptotic precursor neurons, whereas B6- Casp3 -/- cells, which can fragment their DNA, show higher levels of caspase-7 expression and activation. (jneurosci.org)
  • The zymogen feature of caspase-3 is necessary because if unregulated, caspase activity would kill cells indiscriminately. (wikipedia.org)
  • This is the first in vivo demonstration that the "effector" caspase 3 plays an "initiator" role in the regulation of caspase 9. (elsevier.com)
  • Using an unbiased caspase-trapping technique in vivo, weisolated active caspase-9 from ischemic rat brain within 1 h of reperfusion. (elsevier.com)
  • In recent times, cyclic alkylaminoluciferin (CycLuc1) ( λ max =604 nm) demonstrated improved detection of targets in vivo by a significantly increased bioluminescence production over D -luciferin 9 . (nature.com)
  • The study aimed to investigate the effects of FSH and eCG on the ovarian and follicular development, expression levels of FSHR and caspase-9 of ovaries in vivo . (ac.ir)
  • Intended Use Human caspase 9 ELISA Kit allows for the in vitro quantitative determination of caspase 9 , concentrations in serum, Plasma , tissue homogenates and Cell culture supernates and Other biological fluids. (biobool.com)
  • Inquiry About Human caspase 9 ELISA Kit If you hope to order it or contact us directly, please contact us via [email protected] (biobool.com)
  • Furthermore, Bcl-X L failed to inhibit caspase-9 processing mediated by a constitutively active Apaf-1 mutant, suggesting that Bcl-X L regulates caspase-9 through Apaf-1. (pnas.org)
  • I further show that two short peptides derived from these motifs are sufficient to inhibit caspase-9 and NLRP1, respectively. (escholarship.org)
  • Certain diseases involving caspase-9 are treated with therapy by targeting this enzyme. (wikipedia.org)
  • The liver, pancreas, and skeletal muscle express this enzyme at a moderate level, and all other tissues express caspase-9 at low levels. (wikipedia.org)
  • 1998). Enzymatic activity of two caspases related to interleukin-1beta-converting enzyme. (anaspec.com)
  • 2000). Caspase 8: an efficient method for large-scale autoactivation of recombinant procaspase 8 by matrix adsorption and characterization of the active enzyme. (anaspec.com)
  • Furthermore, an interaction was discovered between CARD and the catalytic core of caspase-9 in the presence of a properly formed substrate binding groove, a potential mechanism utilized by the apoptosome for activation of the enzyme. (umass.edu)
  • All in all, the regulation of caspase-9 occurs on a variety of levels that requires almost every surface of the enzyme. (umass.edu)
  • Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. (genetex.com)
  • Structure of caspase-1 (CASP1), originally called interleukin-1 beta-converting enzyme (ICE), the first human caspase to be identified. (wikipedia.org)
  • The active enzyme often exists as a heterotetramer in the biological environment, where a pro-caspase dimer is cleaved together to form a heterotetramer. (wikipedia.org)
  • One unit is defined as the amount of enzyme that cleaves 1nmol of the caspase substrate LEHD-pNA per hour at 37°C in a reaction solution containing 50mM HEPES, pH 7.2, 50mM NaCl, 0.1% CHAPS, 10mM EDTA, 5% glycerol and 10mM DTT. (vwr.com)
  • We biochemically isolated caspase-7 from B6-caspase-3-null ( Casp3 -/- ) tissues as being the enzyme with caspase-3-like properties and capability of performing a caspase-3 surrogate function, apoptotic DNA fragmentation. (jneurosci.org)
  • In contrast, diabetic sensory neurons had elevated expression of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) in their nuclei, cytoplasm, and proximal axonal segments not overlapping with caspase-3 localization. (diabetesjournals.org)
  • One site closely resembles the catalytic site of other caspases, whereas the second has no 'activation loop', disrupting the catalytic machinery in that particular active site. (wikipedia.org)
  • Within caspase-9's active site, in order for catalytic activity to occur there has to be specific amino acids in the right position. (wikipedia.org)
  • Catalytic properties of the caspases. (anaspec.com)
  • This is supported by survival data from a mouse model of apoptosis driven by Sindbis virus expressing either p35 or a catalytic mutant of caspase-9. (biochemj.org)
  • The catalytic site of caspase-3 involves the sulfohydryl group of Cys-163 and the imidazole ring of His-121. (wikipedia.org)
  • This specificity allows caspases to be incredibly selective, with a 20,000-fold preference for aspartic acid over glutamic acid. (wikipedia.org)
  • Caspase 3 and caspase 7 share similar substrate specificity by recognizing tetra-peptide motif Asp-x-x-Asp. (wikipedia.org)
  • pNA (4-nitroaniline)-derived caspase substrates are widely used for the colorimetric detection of various caspase activities. (anaspec.com)
  • Under normal circumstances, caspases recognize tetra-peptide sequences on their substrates and hydrolyze peptide bonds after aspartic acid residues. (wikipedia.org)
  • Apaf-3 was identified as a member of the caspase family, caspase-9. (nih.gov)
  • Caspase-9 is an important member of the caspase family. (antibody-antibodies.com)
  • These results suggested that Tpl2 directly involved in apoptotic signal at the level of caspase-3 activation downstream of caspase-9, and that Tpl2 contributed to the exaggerated of ischemic liver injury through induction of apoptosis. (ajbm.net)
  • Caspases: key players in programmed cell death. (anaspec.com)
  • Biochemical analyses of CED-3, CED-4, and CED-9 have provided insight into the mechanism by which programmed cell death is regulated in the nematode. (pnas.org)
  • caspase-9 plays a central role in cell death through an array of apoptosis inducers-e.g. (thefreedictionary.com)
  • In contrast to T47D cell lines, MCF7 cell lines with tiliroside of 50 [micro]g/ml occurred weak expression of Caspase 8 (Figure 6) moreover Caspase 9 was not expressed. (thefreedictionary.com)
  • However, it has become clear that specific caspases also have functions independent of cell death. (sigmaaldrich.com)
  • Description Human and some mouse caspases are active in apoptosis and cell death and even in necrosis and inflammation. (gentaur.com)
  • D609 enhanced caspase-independent ceramide increase and cell death in response to FasL. (mdpi.com)
  • We recommend a final concentration of 2-10µM for inhibiting caspase activity in cell culture. (scbt.com)
  • Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. (genetex.com)
  • However, increases in caspase-9 activity ranged from 4- to 9-fold in the eight cell lines after treatment with resveratrol. (aacrjournals.org)
  • These collective results suggest that oridonin targets caspase-9 to alter ROS production and autophagy situation to promote HEp-2 cell apoptosis. (spandidos-publications.com)
  • Polycaspase and Caspase in vitro apoptosis kits make it easy to measure cell death and apoptosis in cultured neurons and many other cell types. (neuromics.com)
  • Ptc triggers caspase-9 activation and enhances cell death through a caspase-9-dependent mechanism. (inserm.fr)
  • Note: Background reading from cell lysates and buffers should be subtracted from the readings of both induced and the uninduced samples before calculating fold increase in caspase activity. (antibody-antibodies.com)
  • Activation of Caspases ensures that the cellular components are degraded in a controlled manner, carrying out cell death with minimal effect on surrounding tissues . (wikipedia.org)
  • Caspases have other identified roles in programmed cell death such as pyroptosis and necroptosis . (wikipedia.org)
  • There are other identified roles of caspases such as cell proliferation, tumour suppression, cell differentiation, neural development and axon guidance and ageing. (wikipedia.org)
  • [5] Conversely, over-activation of some caspases such as caspase -3 can lead to excessive programmed cell death. (wikipedia.org)
  • [5] The integral role caspases play in cell death and disease has led to research on using caspases as a drug target. (wikipedia.org)
  • Most caspases play a role in programmed cell death. (wikipedia.org)
  • Caspase-14 plays a role in epithelial cell keratinocyte differentiation and can form an epidermal barrier that protects against dehydration and UVB radiation. (wikipedia.org)
  • Caspase-9 is activated during programmed cell death and cleaves procaspase-7 and procaspase-3. (apexbt.com)
  • We also identified increased caspase-3, -8, and -9 activities in RK13 cell, and an increased Bax to Bcl2 mRNA ratio. (frontiersin.org)
  • The CARD domain of ARC exhibited significant homology to the prodomains of apical caspases and the CARDs present in the cell death regulators Apaf-1 and RAIDD. (pnas.org)
  • Finally, caspase-independent cell death mechanisms might abrogate the selection pressure for caspase inactivation during tumor development. (mdpi.com)
  • Moreover, experimental evidence suggests that caspases might play non-apoptotic roles in processes that are crucial for tumorigenesis, such as cell proliferation, migration, or invasion. (mdpi.com)
  • A key feature of caspases in the cell is that they are present as zymogens, termed procaspases, which are inactive until a biochemical change causes their activation. (wikipedia.org)
  • This broad range indicates that caspase-3 will be fully active under normal and apoptotic cell conditions. (wikipedia.org)
  • Caspase-3 is activated in the apoptotic cell. (wikipedia.org)
  • Caspase-3 activation is a cell requirement during early stages of the skeletal myoblast differentiation. (wikipedia.org)
  • Caspase signals resulting from the activation of nuclease CAD indicate that the cell differentiation is due to a CAD modification in chromatin structure. (wikipedia.org)
  • Our results are consistent with a mechanism in which ligands for the BIR3 domain of XIAP induce apoptosis by freeing up caspases. (rcsb.org)
  • Phosphorylation at Thr 125 is sufficient to block caspase-9 processing and subsequent caspase-3 activation. (nih.gov)
  • FADD, caspase 1, 3, 8, and 9 mRNA was quantified with quantitative real-time polymerase chain reaction (qRT-PCR). (pubmedcentralcanada.ca)
  • FADD, caspase 1, 3 and 8 mRNA copy numbers were not significantly different between patients who died and those discharged from the ICU on either day 1 or day 7 of admission. (pubmedcentralcanada.ca)
  • Expression of caspase 8, caspase 9 and Thy1.1 mRNA was determined by real-time PCR. (arvojournals.org)
  • No change in caspase 8 or caspase 9 mRNA was seen in photoreceptors in glaucoma eyes and no Thy1.1 mRNA was detected in photoreceptors in any eyes. (arvojournals.org)
  • These data show that changes of caspase 8, caspase 9, and Thy1.1 mRNA occur specifically in RGC in experimental glaucoma. (arvojournals.org)
  • Increasing evidence points to the functional importance of alternative splice variations in cancer pathophysiology with the alternative pre-mRNA processing of caspase 9 as one example. (aacrjournals.org)
  • Specifically, the pre-mRNA sequence of caspase 9 was analyzed for RNA cis -elements known to interact with SRSF1, a required enhancer for caspase 9 RNA splicing. (aacrjournals.org)
  • Caspase-9 mRNA in FSH and eCG groups was less than CG. (ac.ir)
  • FSH and eCG inhibited the expression of ovarian caspase-9 mRNA. (ac.ir)
  • These experiments demonstrate that Bcl-X L associates with caspase-9 and Apaf-1, and show that Bcl-X L inhibits the maturation of caspase-9 mediated by Apaf-1, a process that is evolutionarily conserved from nematodes to humans. (pnas.org)
  • HAX-1 inhibits apoptosis in prostate cancer through the suppression of caspase-9 activation. (nih.gov)
  • Each caspase contains conserved residues important for specific proteolytic activity cleaving after aspartic acid residues ( 13 ). (pnas.org)
  • Each caspase contains conserved sequences important for proteolytic activity cleaving after specific aspartic acid residues ( 6 ). (pnas.org)
  • DFFA is encoded by an alternatively encrypted mRNAs originating two distinct forms: short (ICAD-S) and long (ICAD-L), which act like a specific chaperone ensuring the correct CAD's folding Besides, it contains two aspartic acid residues (Asp117 and Asp224) where CAD is identified and, consequently, it stays bounded until Caspase-3 splits this union. (wikipedia.org)
  • Caspase-9 reduced sensitivity to apoptotic stimuli through reactive oxygen species (ROS)-suppressing and autophagy-promoting methods. (spandidos-publications.com)
  • Caspases have been shown to play a crucial role in apoptosis induced by various deleterious and physiologic stimuli. (abcam.cn)
  • Thus, the genomic sequences reported here contain not only the basal promoter of rat caspase-9 but also regulatory elements responsive to pathophysiological stimuli including hypoxia. (elsevier.com)
  • The Patched dependence receptor triggers apoptosis through a DRAL-caspase-9 complex. (inserm.fr)
  • DFFA is the substrate for caspase-3 and triggers DNA fragmentation during apoptosis. (wikipedia.org)
  • The processed caspase-9 stays bound to the apoptosome complex, forming a holoenzyme. (wikipedia.org)
  • Caspase-9 contains a Caspase Activation and Recruitment Domain (CARD), which enables caspase-9 to form a tight interaction with the apoptosome, a heptameric activating platform. (biochemj.org)
  • The caspase-9 CARD has been thought to be principally involved in recruitment to the apoptosome, but its roles outside this interaction have yet to be uncovered. (biochemj.org)
  • Tight regulation of caspase-9, a key initiator of apoptosis, is required to uphold cellular homeostasis. (umass.edu)
  • Together these findings provide mechanistic insight into a new level of caspase-9 regulation, prompting speculation that the CARD may also play a role in the recruitment or recognition of substrate. (biochemj.org)
  • Little is known about the regulation of caspase activity during apoptosis. (pnas.org)
  • Overall, we have identified a novel intronic splicing enhancer that regulates caspase 9 RNA splicing and specifically interacts with SRSF1. (aacrjournals.org)
  • Active caspase-9 works as an initiating caspase by cleaving, thus activating downstream executioner caspases, initiating apoptosis. (wikipedia.org)
  • Executioner caspases have only rarely been found mutated or silenced, and also initiator caspases are only affected in particular types of cancer. (mdpi.com)
  • The presence of the large or small subunits in western blots is considered to be a marker of caspase activation. (novusbio.com)
  • Intracellularly, caspases exist as inactive zymogens (procaspases) that have NH 2 -terminal prodomains plus large and small catalytically active subunits. (aacrjournals.org)
  • Cleavages at Asp-315 by granzyme B and at Asp-330 by caspase-3 generate the two active subunits. (abcam.cn)
  • The caspases are synthesized as inactive precursors that are proteolytically processed to generate active subunits. (pnas.org)
  • Caspases are synthesized as inactive proenzymes and proteolytically processed to form an active complex composed of two heterodimeric subunits of ∼10 and 20 kD. (rupress.org)
  • Caspase-3, in particular, (also known as CPP32/Yama/apopain) is formed from a 32 kDa zymogen that is cleaved into 17 kDa and 12 kDa subunits. (wikipedia.org)
  • In humans, dysfunctional Caspase 9 expression vary from tissue to tissue. (fishersci.com)
  • It can be expected that caspases are involved in additional processes during organogenesis and tissue formation, both in the adult and in the embryo. (biologists.org)